BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 p...BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.展开更多
This review aims to sum up how Non-coding RNAs(ncRNAs)regulate the development of periodontitis and provides a new perspective for understanding the pathogenesis of periodontitis.We explored the ncRNA's dual role ...This review aims to sum up how Non-coding RNAs(ncRNAs)regulate the development of periodontitis and provides a new perspective for understanding the pathogenesis of periodontitis.We explored the ncRNA's dual role in the development of periodontitis by summarizing evidence from previous in vivo and in vitro studies as well as clinical samples.In our review,the downregulation of 18 miRNAs,22 lncRNAs and 10 circRNAs demonstrates protective roles in periodontitis.In contrast,the expression of other 11 miRNAs,7 lncRNAs and 6 circRNAs are upregulated in periodontitis,which promote the progression of periodontitis.These dysregulated ncRNAs exert their protective or destructive roles by mainly influencing cell proliferation,differentiation and apoptosis via cross-talking with various molecules or signaling pathways.Our findings suggested which and how ncRNAs promote or delay the progression of periodontitis,which may greatly contribute to diagnose and therapy development of periodontitis based on ncRNAs in the future.展开更多
Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mec...Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mechanisms have been extensively investigated in recent years.Among these,oxidative stress,inflammatory responses,immunoreactions,and cell death are the most studied.Non-coding RNAs(ncRNAs)are defined as the RNAs that do not encode proteins,but can regulate gene expressions.In recent years,ncRNAs have emerged as research hotspots for various diseases.During the progression of HIRI,ncRNAs are differentially expressed,while these dysregulations of ncRNAs,in turn,have been verified to be related to the above pathological processes involved in HIRI.ncRNAs mainly contain microRNAs,long ncRNAs,and circular RNAs,some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity,and as therapeutic targets to attenuate HIRI.Here,we briefly summarize the common pathophysiology of HIRI,describe the current knowledge of ncRNAs involved in HIRI in animal and human studies,and discuss the potential of ncRNA-targeted therapeutic strategies.Given the scarcity of clinical trials,there is still a long way to go from pre-clinical to clinical application,and further studies are needed to uncover their potential as therapeutic targets.展开更多
Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that res...Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.展开更多
Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that w...Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that widely cultured in the coastal areas of China,Japan,and South Korea.With the expansion of aquacultural scale,various pathogens have threatened its industry and reduced its economic values.It has been reported that lncRNA were involved in the immune response and metabolic pathway in teleost,while no study is available on identification and functional analysis of lncRNAs in black rockfish so far.Herein,this study was performed to identify lncRNAs in the intestine of black rockfish after Edwardsiella tarda infection.In our results,a total of 9311 lncRNAs were identified through highthroughput sequencing,and 102 lncRNAs were significantly regulated following challenge,which were predicted to target 3348 mRNAs.Results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the se target genes showed they were function in catalytic activity,hydrolase activity,defense response and peptidase activity,which involved in metabolic pathways and immune related pathways.In addition,47 lncRNAs and 8 differentially expressed mRNAs(DEmRNAs)showed co-expression at two or more infection time points with metabolism and immunity functions.Moreover,real-time quantitative PCR(qRT-PCR)was performed to verify the reliability of sequencing gene expression analysis results.This research laid the foundation for further investigation of the regulatory roles of lncRNAs in the intestinal immune response of black rockfish.展开更多
Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorp...Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorphism in haploid gametophytes.The sex of Saccharina japonica gametophytes is determined by UV sexual system.However,no results have been reported on the lncRNAs involved in the sex-related gene regulation of S.japonica.This study identified a number of lncRNAs and assessed their expression levels in male and female gametophytes.Among them,a total of 405 lncRNAs and 211 mRNAs showed differential expressions.Furthermore,the functions of target genes of differentially expressed lncRNAs(DELs)differed from those of differentially expressed genes(DEGs),suggesting that lncRNA may interact with other functional proteins,in addition to DEGs,to involve sex regulation in S.japonica.There were 32 and 90 potential cis-regulatory and trans-regulatory interactions between DELsDEGs,respectively.Five of these lncRNAs(LNC_002974,LNC_021059,LNC_038466,LNC_051584,and LNC_027400)interacted with putative male sex determination region(SDR)genes,suggesting that they act as regulators in gametophytes'sex regulation potentially.Findings from this study contribute to our understanding of the roles of lncRNAs in sex differentiation and lay the foundation for functional studies of candidate lncRNAs in the future.展开更多
Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for ...Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.展开更多
Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,...Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,may also be involved in temperature-affected fruit senescence.Based on the transcriptome and microRNA sequencings,in this study,3330 lncRNAs were isolated from Pyrus pyrifolia fruit.Of these lncRNAs,2060 and 537 were responsive to high-and low-temperature conditions,respectively.Of these differentially expressed lncRNAs,82 and 24 correlated to the mRNAs involved in fruit senescence under high-and low-temperature conditions,respectively.Moreover,three lncRNAs were predicted to be competing endogenous RNAs(ceRNAs)that interact with the microRNAs involved in fruit senescence,while one and two ceRNAs were involved in fruit senescence under high-and low-temperature conditions,respectively.A dual-luciferase assay showed that the interaction of an lncRNA with a microRNA disrupts the action of the microRNA on the expression of its target mRNA(s).Furthermore,four alternative splicing-derived lncRNAs interacted with miR172i homologies(Novel_88 and Novel_69)to relieve the repressed expression of their target and produce an miR172i precursor.Correlation analysis of microRNA expression suggested that Novel_69 is likely involved in the cleavage of the pre-miR172i hairpin to generate mature miR172i.Taken together,lncRNAs are involved in pear fruit senescence under high-or low-temperature conditions through ceRNAs and the production of microRNA.展开更多
Non-coding RNAs are speculated to exert important regulatory functions at the level of gene expression,oncogenesis,and many other pathologies.Hepatitis B virus(HBV)infection is a leading cause of hepatocellular carcin...Non-coding RNAs are speculated to exert important regulatory functions at the level of gene expression,oncogenesis,and many other pathologies.Hepatitis B virus(HBV)infection is a leading cause of hepatocellular carcinoma(HCC),and some studies have shown that the expression of non-coding RNAs has an assignable effect on the development of HBV-induced HCC.In this context,the functions and molecular mechanisms of the HBVinduced non-coding RNA expression in the development of hepatoma have attracted increasing attention.This review covers the progress in the exploration of the relationship between HBV-induced hepatoma and non-coding RNA expression,cataloging the recent reports about the roles of non-coding RNAs in HBV-induced hepatoma into five classes,including(1)modulation of metabolism in hepatic cancer,(2)aggravation of inflammation and hepatic fibrosis,(3)alteration of the tumor immune microenvironment,(4)non-coding RNA N6-methyladenosine modification,and a seemingly opposite process,(5)the suppression of the progression of HBV-related HCC.All evidence supports non-coding RNAs as promising novel targets for the early diagnosis and treatments for HCC.展开更多
BACKGROUND Our previous study reported that the single-nucleotide polymorphism(SNP)rs155979 GC in the promoter region of long-chain non-coding RNA(lncRNA)NONHSAT102891 affects depression susceptibility in a Chinese po...BACKGROUND Our previous study reported that the single-nucleotide polymorphism(SNP)rs155979 GC in the promoter region of long-chain non-coding RNA(lncRNA)NONHSAT102891 affects depression susceptibility in a Chinese population.AIM To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population.METHODS This this case-control association study was approved by the Ethics Committee of Chengdu Medical College(approval number:201815).Patient diagnosis was based on DSM-IV criteria.We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology,and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects.The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells.RESULTS Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times[TC/CC vs TT:odds ratio(OR)=1.59,95%confidence interval(CI):1.08-2.35,P=0.019].The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230,and the double SNP CG haplotype was more common in the control group compared to case group,indicating that this haplotype significantly reduced the risk of depression(C/G vs T/A:OR=0.42,95%CI:0.21-0.83,P=0.01).There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group(P>0.05),indicating that the double SNP haplotype has no transcrip-tional activity.CONCLUSION The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.展开更多
Osteomyelitis is a debilitating bone infection primarily caused by Staphylococcus aureus.Despite advancements in surgery and chemotherapy,the treatment of osteomyelitis remains unsatisfactory,characterized by antibiot...Osteomyelitis is a debilitating bone infection primarily caused by Staphylococcus aureus.Despite advancements in surgery and chemotherapy,the treatment of osteomyelitis remains unsatisfactory,characterized by antibiotic resistance and recurrent relapses.Numerous studies have confirmed that non-coding RNAs could play an emerging role in regulating gene expression,as well as in the differentiation of osteoblasts and osteoclasts,along with bone formation.In this context,we provide an overview of current knowledge regarding the roles of non-coding RNAs in osteomyelitis and explore the potential therapeutic applications of these molecules in disease management,aiming to uncover novel diagnostic and treatment approaches.展开更多
Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic a...Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.展开更多
Gastrointestinal stromal tumors(GISTs)are considered the model solid malignancies of targeted therapy after the discovery of imatinib effectiveness against their tyrosine kinase inhibitors.Non-coding RNAs are molecule...Gastrointestinal stromal tumors(GISTs)are considered the model solid malignancies of targeted therapy after the discovery of imatinib effectiveness against their tyrosine kinase inhibitors.Non-coding RNAs are molecules with no protein coding capacity that play crucial role to several biological steps of normal cell proliferation and differentiation.When the expression of these molecules found to be altered it seems that they affect the process of carcinogenesis in multiple ways,such as proliferation,apoptosis,differentiation,metastasis,and drug resistance.This review aims to provide an overview of the latest research papers and summarize the current evidence about the role of non-coding RNAs in pathogenesis of GISTs,including their potential clinical applications.展开更多
AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were d...AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.展开更多
Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and ...Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.展开更多
Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer rese...Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.展开更多
BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essent...BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.展开更多
BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To exp...BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.METHODS CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR(qRT-PCR).CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay.In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.RESULTS CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines(P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC(P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion,migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1(CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5 p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5 p reversed the effect of CASC19 on cellproliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.CONCLUSION CASC19 positively regulates CEMIP expression through targeting miR-140-5 p.CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.展开更多
Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expressi...Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.展开更多
Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The pr...Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.展开更多
基金Natural Science Foundation of Shandong Province,No.ZR2020MH207 and No.ZR2020MH251.
文摘BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.
基金supported by Guizhou Provincial Science and Technology Foundation(Grant No.[2020]1Y292)Science and technology fund project of Guizhou Provincial Health Commission(NO:gzwkj2023-201)+1 种基金Doctor Startup Foundation of Zunyi Medical University(Grant No.[2017]5733-044)Zunyi Oral Disease Immune Prevention and Medical Biomaterials Research and Development Innovation Talent Team,Zunyi Science Talent[2022]No.1.
文摘This review aims to sum up how Non-coding RNAs(ncRNAs)regulate the development of periodontitis and provides a new perspective for understanding the pathogenesis of periodontitis.We explored the ncRNA's dual role in the development of periodontitis by summarizing evidence from previous in vivo and in vitro studies as well as clinical samples.In our review,the downregulation of 18 miRNAs,22 lncRNAs and 10 circRNAs demonstrates protective roles in periodontitis.In contrast,the expression of other 11 miRNAs,7 lncRNAs and 6 circRNAs are upregulated in periodontitis,which promote the progression of periodontitis.These dysregulated ncRNAs exert their protective or destructive roles by mainly influencing cell proliferation,differentiation and apoptosis via cross-talking with various molecules or signaling pathways.Our findings suggested which and how ncRNAs promote or delay the progression of periodontitis,which may greatly contribute to diagnose and therapy development of periodontitis based on ncRNAs in the future.
基金the National Natural Science Foundation of China,No.82070648the Science and Technology Innovation Program of Hunan Province,No.2021SK4014.
文摘Hepatic ischemia-reperfusion injury(HIRI)is the major complication of liver surgery and liver transplantation,that may increase the postoperative morbidity,mortality,tumor progression,and metastasis.The underlying mechanisms have been extensively investigated in recent years.Among these,oxidative stress,inflammatory responses,immunoreactions,and cell death are the most studied.Non-coding RNAs(ncRNAs)are defined as the RNAs that do not encode proteins,but can regulate gene expressions.In recent years,ncRNAs have emerged as research hotspots for various diseases.During the progression of HIRI,ncRNAs are differentially expressed,while these dysregulations of ncRNAs,in turn,have been verified to be related to the above pathological processes involved in HIRI.ncRNAs mainly contain microRNAs,long ncRNAs,and circular RNAs,some of which have been reported as biomarkers for early diagnosis or assessment of liver damage severity,and as therapeutic targets to attenuate HIRI.Here,we briefly summarize the common pathophysiology of HIRI,describe the current knowledge of ncRNAs involved in HIRI in animal and human studies,and discuss the potential of ncRNA-targeted therapeutic strategies.Given the scarcity of clinical trials,there is still a long way to go from pre-clinical to clinical application,and further studies are needed to uncover their potential as therapeutic targets.
文摘Aging is linked to the deterioration of many physical and cognitive abilities and is the leading risk factor for Alzheimer’s disease. The growing aging population is a significant healthcare problem globally that researchers must investigate to better understand the underlying aging processes. Advances in microarrays and sequencing techniques have resulted in deeper analyses of diverse essential genomes(e.g., mouse, human, and rat) and their corresponding cell types, their organ-specific transcriptomes, and the tissue involved in aging. Traditional gene controllers such as DNA-and RNA-binding proteins significantly influence such programs, causing the need to sort out long non-coding RNAs, a new class of powerful gene regulatory elements. However, their functional significance in the aging process and senescence has yet to be investigated and identified. Several recent researchers have associated the initiation and development of senescence and aging in mammals with several well-reported and novel long non-coding RNAs. In this review article, we identified and analyzed the evolving functions of long non-coding RNAs in cellular processes, including cellular senescence, aging, and age-related pathogenesis, which are the major hallmarks of long non-coding RNAs in aging.
基金Supported by the Young Experts of Taishan Scholars(No.tsqn201909130)the Science and Technology Support Plan for Youth Innovation of Colleges and Universities in Shandong Province(No.2019KJF003)+1 种基金the“First Class Fishery Discipline”Program in Shandong Province,a special talent program“One Matter One Decision(Yi Shi Yi Yi)”Program in Shandong Province,Chinathe Breeding Plan of Shandong Provincial Qingchuang Research Team(2019)。
文摘Long non-coding RNAs(lncRNAs)are a class of transcripts longer than 200 bp,which have been emerged as essential regulators in numerous biological processes.Black rockfish(Sebastes schlegelii)is an economic fish that widely cultured in the coastal areas of China,Japan,and South Korea.With the expansion of aquacultural scale,various pathogens have threatened its industry and reduced its economic values.It has been reported that lncRNA were involved in the immune response and metabolic pathway in teleost,while no study is available on identification and functional analysis of lncRNAs in black rockfish so far.Herein,this study was performed to identify lncRNAs in the intestine of black rockfish after Edwardsiella tarda infection.In our results,a total of 9311 lncRNAs were identified through highthroughput sequencing,and 102 lncRNAs were significantly regulated following challenge,which were predicted to target 3348 mRNAs.Results of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the se target genes showed they were function in catalytic activity,hydrolase activity,defense response and peptidase activity,which involved in metabolic pathways and immune related pathways.In addition,47 lncRNAs and 8 differentially expressed mRNAs(DEmRNAs)showed co-expression at two or more infection time points with metabolism and immunity functions.Moreover,real-time quantitative PCR(qRT-PCR)was performed to verify the reliability of sequencing gene expression analysis results.This research laid the foundation for further investigation of the regulatory roles of lncRNAs in the intestinal immune response of black rockfish.
基金supported by the National Natural Science Foundation of China(No.132072962)the Agricultural Industrial Technology System in Shandong Province(No.SDAIT-26)+3 种基金the‘First Class Fishery Discipline’Programme[(2020)3]in Shandong Provincethe Special Talent Programme‘Yishi Yiyi’in Shandong Province,Chinathe National Key R&D Program of China(No.2018YFD0901500)the Shandong Province Agriculture Seed Project(No.2021LZ GC004)。
文摘Long non-coding RNAs(lncRNAs)regulate a variety of biological processes,including sexual reproduction and differentiation.Saccharina japonica,a commercially important brown alga in China,shows remarkable sexual dimorphism in haploid gametophytes.The sex of Saccharina japonica gametophytes is determined by UV sexual system.However,no results have been reported on the lncRNAs involved in the sex-related gene regulation of S.japonica.This study identified a number of lncRNAs and assessed their expression levels in male and female gametophytes.Among them,a total of 405 lncRNAs and 211 mRNAs showed differential expressions.Furthermore,the functions of target genes of differentially expressed lncRNAs(DELs)differed from those of differentially expressed genes(DEGs),suggesting that lncRNA may interact with other functional proteins,in addition to DEGs,to involve sex regulation in S.japonica.There were 32 and 90 potential cis-regulatory and trans-regulatory interactions between DELsDEGs,respectively.Five of these lncRNAs(LNC_002974,LNC_021059,LNC_038466,LNC_051584,and LNC_027400)interacted with putative male sex determination region(SDR)genes,suggesting that they act as regulators in gametophytes'sex regulation potentially.Findings from this study contribute to our understanding of the roles of lncRNAs in sex differentiation and lay the foundation for functional studies of candidate lncRNAs in the future.
基金The Natural Science Foundation of Shandong Province,No.ZR2020MH238.
文摘Colorectal cancer(CRC)is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs(ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation,and by epigenetic modification.In this review,we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin.Furthermore,we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy.This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.
基金supported by the Fundamental Research Funds for the Central Universities(Grant No.KYYJ202116)the Jiangsu Agricultural Science and Technology Innovation Fund[Grant No.CX(20)2020]the Earmarked Fund for China Agriculture Research System(Grant No.CARS-28).
文摘Pear fruit senescence under high-and low-temperature conditions has been reported to be mediated by microRNAs.Long non-coding RNAs(lncRNAs),which can function as competing endogenous RNAs that interact with microRNAs,may also be involved in temperature-affected fruit senescence.Based on the transcriptome and microRNA sequencings,in this study,3330 lncRNAs were isolated from Pyrus pyrifolia fruit.Of these lncRNAs,2060 and 537 were responsive to high-and low-temperature conditions,respectively.Of these differentially expressed lncRNAs,82 and 24 correlated to the mRNAs involved in fruit senescence under high-and low-temperature conditions,respectively.Moreover,three lncRNAs were predicted to be competing endogenous RNAs(ceRNAs)that interact with the microRNAs involved in fruit senescence,while one and two ceRNAs were involved in fruit senescence under high-and low-temperature conditions,respectively.A dual-luciferase assay showed that the interaction of an lncRNA with a microRNA disrupts the action of the microRNA on the expression of its target mRNA(s).Furthermore,four alternative splicing-derived lncRNAs interacted with miR172i homologies(Novel_88 and Novel_69)to relieve the repressed expression of their target and produce an miR172i precursor.Correlation analysis of microRNA expression suggested that Novel_69 is likely involved in the cleavage of the pre-miR172i hairpin to generate mature miR172i.Taken together,lncRNAs are involved in pear fruit senescence under high-or low-temperature conditions through ceRNAs and the production of microRNA.
基金This work was supported by the Key Research&Development Plan of Zhejiang Province(2019C04005)the National Key Research and Development Program of China(2018YFC2000500).
文摘Non-coding RNAs are speculated to exert important regulatory functions at the level of gene expression,oncogenesis,and many other pathologies.Hepatitis B virus(HBV)infection is a leading cause of hepatocellular carcinoma(HCC),and some studies have shown that the expression of non-coding RNAs has an assignable effect on the development of HBV-induced HCC.In this context,the functions and molecular mechanisms of the HBVinduced non-coding RNA expression in the development of hepatoma have attracted increasing attention.This review covers the progress in the exploration of the relationship between HBV-induced hepatoma and non-coding RNA expression,cataloging the recent reports about the roles of non-coding RNAs in HBV-induced hepatoma into five classes,including(1)modulation of metabolism in hepatic cancer,(2)aggravation of inflammation and hepatic fibrosis,(3)alteration of the tumor immune microenvironment,(4)non-coding RNA N6-methyladenosine modification,and a seemingly opposite process,(5)the suppression of the progression of HBV-related HCC.All evidence supports non-coding RNAs as promising novel targets for the early diagnosis and treatments for HCC.
基金Supported by National Natural Science Foundation of China,No.81901379Chengdu Medical College Graduate Research Innovation Fund Project,No.YCX2023-01-03National Undergraduate Training Program for Innovation and Entrepreneurship,No.202113705034.
文摘BACKGROUND Our previous study reported that the single-nucleotide polymorphism(SNP)rs155979 GC in the promoter region of long-chain non-coding RNA(lncRNA)NONHSAT102891 affects depression susceptibility in a Chinese population.AIM To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population.METHODS This this case-control association study was approved by the Ethics Committee of Chengdu Medical College(approval number:201815).Patient diagnosis was based on DSM-IV criteria.We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology,and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects.The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells.RESULTS Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times[TC/CC vs TT:odds ratio(OR)=1.59,95%confidence interval(CI):1.08-2.35,P=0.019].The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230,and the double SNP CG haplotype was more common in the control group compared to case group,indicating that this haplotype significantly reduced the risk of depression(C/G vs T/A:OR=0.42,95%CI:0.21-0.83,P=0.01).There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group(P>0.05),indicating that the double SNP haplotype has no transcrip-tional activity.CONCLUSION The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.
基金supported by National Natural Science Foundation of China(32271177,82003981 to ZQ)President Fund of the 960th Hospital of Joint Logistics Support Force(2017ZX05 to C-LS).
文摘Osteomyelitis is a debilitating bone infection primarily caused by Staphylococcus aureus.Despite advancements in surgery and chemotherapy,the treatment of osteomyelitis remains unsatisfactory,characterized by antibiotic resistance and recurrent relapses.Numerous studies have confirmed that non-coding RNAs could play an emerging role in regulating gene expression,as well as in the differentiation of osteoblasts and osteoclasts,along with bone formation.In this context,we provide an overview of current knowledge regarding the roles of non-coding RNAs in osteomyelitis and explore the potential therapeutic applications of these molecules in disease management,aiming to uncover novel diagnostic and treatment approaches.
基金This study was funded by the Natural Science Foundation of Shanghai of China(No.20ZR1452300)National Natural Science Foundation of China(No.81874201)+1 种基金Shanghai Municipal Health Commission Foundation(No.201840359)Natural Science Foundation of Shanghai(No.20ZR1452500).
文摘Background:Long non-coding RNAs(lncRNAs)play a vital role in autophagy modulation and tumor progression.However,the key lncRNAs and their functions in gastric cancer(GC)remain largely unknown.Methods:A bioinformatic analysis of GC patients’gene expression profiling data from the Cancer Genome Atlas database was performed to identify autophagy-related lncRNAs that are associated with predictive risk.Through Cox regression and Lasso regression analyses,the autophagy-related lncRNAs that are associated with prognosis were identified,and a novel prognostic model for GC was established.The model was then used to evaluate the clinical features and predictive risk of individuals with GC.By using two datasets,GSE 62254(n=300)and GSE 15459(n=192),from Gene Expression Omnibus,its effectiveness was verified.Gene set enrichment analysis according to hallmark and Kyoto Encyclopedia of Genes and Genomes were used to determine the possible biological roles of these lncRNAs.Furthermore,the HOXD antisense growth-associated long non-coding RNA(HAGLR)mechanism in GC was discovered through in vitro and in vivo experiments.Results:Six lncRNAs associated with autophagy in GC were identified,and a new prognostic risk model based on these lncRNAs was established.The six-lncRNA signature was significantly associated with adverse clinicopathological features and found to be an independent GC prognostic factor.The model was proven to be effective and robust by GSE62254 and GSE15459.According to gene set enrichment analysis,the six lncRNAs appeared to be tightly linked to autophagy-related and cancer-related mechanisms.HAGLR was also found to promote tumor growth by enhancing autophagy signaling in GC.Conclusion:A novel prognostic model integrating HAGLR that can effectively evaluate and predict the prognostic risk of GC patients was established.The results indicated that HAGLR promotes gastric cancer progression by enhancing autophagy and is anticipated to be a potential new target for the treatment of gastric cancer.
基金supported by a non-profit organization of Greek Society of Cancer Biomarkers and Targeted Therapy.
文摘Gastrointestinal stromal tumors(GISTs)are considered the model solid malignancies of targeted therapy after the discovery of imatinib effectiveness against their tyrosine kinase inhibitors.Non-coding RNAs are molecules with no protein coding capacity that play crucial role to several biological steps of normal cell proliferation and differentiation.When the expression of these molecules found to be altered it seems that they affect the process of carcinogenesis in multiple ways,such as proliferation,apoptosis,differentiation,metastasis,and drug resistance.This review aims to provide an overview of the latest research papers and summarize the current evidence about the role of non-coding RNAs in pathogenesis of GISTs,including their potential clinical applications.
文摘AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.
基金Supported by the National Research,Development and Innovation Office,No.NVKP_16-1-2016-0004
文摘Long non-coding RNAs(lncRNAs)are members of the non-protein coding RNA family longer than 200 nucleotides.They participate in the regulation of gene and protein expression influencing apoptosis,cell proliferation and immune responses,thereby playing a critical role in the development and progression of various cancers,including colorectal cancer(CRC).As CRC is one of the most frequently diagnosed malignancies worldwide with high mortality,its screening and early detection are crucial,so the identification of disease-specific biomarkers is necessary.LncRNAs are promising candidates as they are involved in carcinogenesis,and certain lncRNAs(e.g.,CCAT1,CRNDE,CRCAL1-4)show altered expression in adenomas,making them potential early diagnostic markers.In addition to being useful as tissue-specific markers,analysis of circulating lncRNAs(e.g.,CCAT1,CCAT2,BLACAT1,CRNDE,NEAT1,UCA1)in peripheral blood offers the possibility to establish minimally invasive,liquid biopsy-based diagnostic tests.This review article aims to describe the origin,structure,and functions of lncRNAs and to discuss their contribution to CRC development.Moreover,our purpose is to summarise lncRNAs showing altered expression levels during tumor formation in both colon tissue and plasma/serum samples and to demonstrate their clinical implications as diagnostic or prognostic biomarkers for CRC.
文摘Gastric cancer(GC) is the fourth most common cancer and the third leading cause of cancer mortality worldwide. Micro RNAs(mi RNAs) and long non-coding RNAs(lnc RNAs) are the most popular non-coding RNAs in cancer research. To date,the roles of mi RNAs and lnc RNAs have been extensively studied in GC,suggesting that mi RNAs and lnc RNAs represent a vital component of tumor biology. Furthermore,circulating mi RNAs and lnc RNAs are found to be dysregulated in patients with GC compared with healthy individuals. Circulating mi RNAs and lnc RNAs may function as promising biomarkers to improve the early detection of GC. Multiple possibilities for mi RNA secretion have been elucidated,including active secretion by microvesicles,exosomes,apoptotic bodies,highdensity lipoproteins and protein complexes as well as passive leakage from cells. However,the mechanism underlying lnc RNA secretion and the functions of circulating mi RNAs and lnc RNAs have not been fully illuminated. Concurrently,to standardize results of global investigations of circulating mi RNAs and lnc RNAs biomarker studies,several recommendations for preanalytic considerations are put forward. In this review,we summarize the known circulating mi RNAs and lnc RNAs for GC diagnosis. The possible mechanism of mi RNA and lnc RNA secretion as well as methodologies for identification of circulating mi RNAs and lnc RNAs are also discussed. The topics covered here highlight new insights into GC diagnosis and screening.
文摘BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy.Poor responses to radiotherapy in most patients generally result in local radiotherapy failure,so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance.The long noncoding RNA(lncRNA)Rpph1 is highly expressed in human gastric cancer tissues,and represses breast cancer cell proliferation and tumorigenesis.However,the expression of lncRNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lncRNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants.The expression of Rpph1 was determined by qRT-PCR.siRNA-NC and siRNA-Rpph1 were transfected into esophageal cancer cell lines,and cells without transfection were designated as the blank control group.Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays.Cell proliferation was assessed by MTT assays,cell apoptosis by flow cytometry,and cell migration by wound-healing assays.Changes in cell cycle distribution were monitored.RESULTS Rpph1 was highly expressed in esophageal carcinoma,making it a promising marker for the diagnosis of esophageal cancer.Rpph1 could also be used to distinguish different short-term responses,T stages,N stages,and clinical stages of esophageal cancer patients.The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P<0.05).In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy,stronger apoptosis in esophageal cancer cells induced by radiotherapy,higher expression of Bax and caspase-3,and lower expression of Bcl-2(Bax,caspase-3,and Bcl-2 are apoptosis-related proteins).Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest,and significantly inhibited the expression of proteins involved in cell proliferation,migration,and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer.Silencing Rpph1 expression can promote cell apoptosis,inhibit cell proliferation and migration,and increase radio-sensitivity.
基金Supported by the National Natural Science Foundation of China,No.81570375
文摘BACKGROUND Long non-coding RNAs(lncRNAs) are widely involved in tumor regulation.Nevertheless, the role of the lncRNA cancer susceptibility 19(CASC19) in colorectal cancer(CRC) has yet to be fully clarified.AIM To explore the effect of CASC19 on proliferation and metastasizing ability of CRC cells.METHODS CASC19 expression in human CRC tissues, pair-matched adjacent normal colon tissues, and CRC cells was detected using quantitative real-time PCR(qRT-PCR).CASC19 expression, as well as its relation to overall survival, was extrapolated by Kaplan-Meier survival analysis together with multivariable Cox regression assay.In vitro experiments were performed to confirm whether CASC19 regulates CRC cell invasion, migration, proliferation, and apoptosis.RESULTS CASC19 expression was markedly upregulated in CRC tissues and CRC cell lines(P < 0.05). qRT-PCR revealed that CASC19 expression was higher in 25 tissue samples from patients with aggressive CRC compared with the 27 tissue samples from patients with nonaggressive CRC(P < 0.05). Higher CASC19 expression was associated with poorer patient prognoses. Furthermore, in vitro experiments demonstrated that CASC19 overexpression enhanced CRC cell invasion,migration, and proliferation. CASC19 overexpression enhanced the expression of cell migration inducing hyaluronidase 1(CEMIP) and epithelial-mesenchymal transition markers. MiR-140-5 p was found to be able to bind directly to CASC19 and CEMIP. Overexpression of miR-140-5 p reversed the effect of CASC19 on cellproliferation and tumor migration, as well as suppressed CASC19-induced CEMIP expression.CONCLUSION CASC19 positively regulates CEMIP expression through targeting miR-140-5 p.CASC19 may possess an oncogenic function in CRC progression, highlighting its potential as an essential biomarker in CRC diagnosis and therapy.
基金Supported by National Natural Science Foundation of China,No.81171660Zhejiang Provincial Natural Science Foundation of China,No.Y14C060003+4 种基金Natural Science Foundation of Ningbo,No.2012A610207The Scientific Innovation Team Project of Ningbo,No.2011B82014The Project of Key Disciplines in Ningbo,No.XKL11D2127 and No.XKL11D2128Foundation of Zhejiang Provincial Key Laboratory of Pathophysiology,No.201301K.C.Wong Magna Fund in Ningbo University
文摘Non-coding RNAs(ncRNAs)play key roles in development,proliferation,differentiation and apoptosis.Altered ncRNA expression is associated with gastric cancer occurrence,invasion,and metastasis.Moreover,aberrant expression of microRNAs(miRNAs)is significantly related to gastric cancer tumor stage,size,differentiation and metastasis.MiRNAs interrupt cellular signaling pathways,inhibit the activity of tumor suppressor genes,and affect the cell cycle in gastric cancer cells.Some miRNAs,including miR-21,miR-106a and miR-421,could be potential markers for the diagnosis of gastric cancer.Long non-coding RNAs (lncRNAs),a new research hotspot among cancerassociated ncRNAs,play important roles in epigenetic,transcriptional and post-transcriptional regulation.Several gastric cancer-associated lncRNAs,such as CCAT1,GACAT1,H19,and SUMO1P3,have been explored.In addition,Piwi-interacting RNAs,another type of small ncRNA that is recognized by gastroenterologists,are involved in gastric carcinogenesis,and piR-651/823represents an efficient diagnostic biomarker of gastric cancer that can be detected in the blood and gastric juice.Small interfering RNAs also function in posttranscriptional regulation in gastric cancer and might be useful in gastric cancer treatment.
文摘Helicobacter pylori(H. pylori) is a model organism for understanding host-pathogen interactions and infection-mediated carcinogenesis. Gastric cancer and H. pylori colonization indicates the strong correlation. The progression and exacerbation of H. pylori infection are influenced by some factors of pathogen and host. Several virulence factors involved in the proper adherence and attenuation of immune defense to contribute the risk of emerging gastric cancer, therefore analysis of them is very important. H. pylori also modulates inflammatory and autophagy process to intensify its pathogenicity. From the host regard, different genetic factors particularly affect the development of gastric cancer. Indeed, epigenetic modifications, Micro RNA and long non-coding RNA received more attention. Generally, various factors related to pathogen and host that modulate gastric cancer development in response to H. pylori need more attention due to develop an efficacious therapeutic intervention. Therefore, this paper will present a brief overview of host-pathogen interaction especially emphases on bacterial virulence factors, interruption of host cellular signaling, the role of epigenetic modifications and non-coding RNAs.
