Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-t...Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.展开更多
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
BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seri...BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.展开更多
BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic canc...BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.展开更多
Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in ...Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in tumor biology,the abnormal expression of long non-coding RNA(lncRNAs)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes.In this study,we identified a novel lncRNA NFIA antisense RNA 1(NFIA-AS1)and explored its role and clinical significance in gastric cancer.Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples.The lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM stage.Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival.We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels.In conclusion,our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.展开更多
Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” wit...Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.展开更多
Background:Long non-coding RNAs(lncRNAs)play key roles in human cancers.In our previous study,we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1(FKBP9P1)was highly expressed in head and neck squamous cel...Background:Long non-coding RNAs(lncRNAs)play key roles in human cancers.In our previous study,we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1(FKBP9P1)was highly expressed in head and neck squamous cell cancer(HNSCC)tissues.However,its functional significance remains poorly understood.In the present study,we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC.Methods:Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues,matched adjacent normal tissues,human HNSCC cells(FaDu,Cal-27,SCC4,and SCC9),and human immortalized keratinocytes cell HaCaT(normal control).Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1,sh-FKBP9P1-2,and normal control(sh-NC)lentivirus.Cell counting kit-8 assay,colony formation assay,wound healing assay,and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells.Furthermore,western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression.Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups.Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test.The comparison between two groups was analyzed by Student t test,and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test.Results:FKBP9P1 expression was significantly up-regulated in HNSCC tissues(tumor vs.normal,1.914 vs.0.957,t=7.746,P<0.001)and cell lines(P<0.01 in all HNSCC cell lines).Besides,the median FKBP9P1 expression of HNSCC tissues(1.677)was considered as the threshold.High FKBP9P1 level was correlated with advanced T stage(P=0.022),advanced N stage(P=0.036),advanced clinical stage(P=0.018),and poor prognosis of HNSCC patients(overall survival,P=0.002 and disease-free survival,P<0.001).Knockdown of FKBP9P1 led to marked repression in proliferation,migration,and invasion of HNSCC cells in vitro(P all<0.01).Mechanistically,silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway.Conclusions:Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT(phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase)signaling in vitro.Therefore,FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.展开更多
Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer...Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer-promoting roles in cancer stem cells.However,the regulatory mechanism of AFAP1-AS1 in cervical cancer(CC)stem cells is unknown.The present study aimed to provide a new therapeutic target for the clinical treatment of CC.Methods:Hyaluronic acid receptor cluster of differentiation 44 variant exon 6(CD44v6)(+)CC cells were isolated by flow cytometry(FCM).Small interfering RNAs of AFAP1-AS1(siAFAP1-AS1)were transfected into the(CD44v6)(+)cells.The levels of AFAP1-AS1 were measured by quantitative real-time PCR(qRT-PCR).Sphere formation assay,cell cycle analysis,and Western blotting were used to detect the effect of siAFAP1-AS1.RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor(VEGF)-C.Results:CD44v6(+)CCcells had remarkable stemness and a high level ofAFAP1-AS1.However,AFAP1-AS1knockdownwithsiAFAP1-AS1suppressed the cell cycle transitionofG(1)/S phase and inhibited self-renewal ofCD44v6(+)CCcells,the levels of the stemnessmarkers octamer-binding transcription factor 4(OCT4),osteopontin(OPN),and cluster of differentiation 133(CD133),and the epithelialmesenchymal transition(EMT)-related proteins Twist1,matrix metalloprotease(MMP)-9,and VEGF-C.In the mechanism study,miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+)CC cells.Conclusions:LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.展开更多
基金supported by the Medical Science and Technology Research Foundation of Guangdong Province(No.A2020559).
文摘Objective This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1(PCED1B-AS1)in the development of hepatocellular carcinoma(HCC).Methods A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients.The interactions of PCED1B-AS1 and microRNA-34a(miR-34a)were detected by dual luciferase activity assay and RNA pull-down assay.The RNA expression levels of PCED1B-AS1,miR-34a and CD44 were detected by RT-qPCR,and the protein expression level of CD44 was determined by Western blotting.The cell proliferation was detected by cell proliferation assay,and the cell invasion and migration by transwell invasion assay.The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study.Results PCED1B-AS1 was highly expressed in HCC tissues,which was associated with poor survival of HCC patients.Furthermore,PCED1B-AS1 interacted with miR-34a in HCC cells,but they did not regulate the expression of each other.Additionally,PCED1B-AS1 increased the expression level of CD44,which was targeted by miR-34a.The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro,while CD44 exhibited the opposite effects.Furthermore,PCED1B-AS1 suppressed the role of miR-34a.Moreover,the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo.Conclusion PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC.
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.
文摘BACKGROUND The incidence of colon cancer(CC)is currently high,and is mainly treated with chemotherapy.Oxaliplatin(L-OHP)is a commonly used drug in chemotherapy;however,long-term use can induce drug resistance and seriously affect the prognosis of patients.Therefore,this study investigated the mechanism of Opainteracting protein 5 antisense RNA 1(OIP5-AS1)on L-OHP resistance by determining the expression of OIP5-AS1 and micro RNA-137(miR-137)in CC cells and the effects on L-OHP resistance,with the goal of identifying new targets for the treatment of CC.AIM To study the effects of long non-coding RNA OIP5-AS1 on L-OHP resistance in CC cell lines and its regulation of miR-137.METHODS A total of 114 CC patients admitted to China-Japan Union Hospital of Jilin University were enrolled,and the expression of miR-137 and OIP5-AS1 in tumor tissues and corresponding normal tumor-adjacent tissues was determined.The influence of OIP5-AS1 and miR-137 on the biological behavior of CC cells was evaluated.Resistance to L-OHP was induced in CC cells,and their activity was determined and evaluated using cell counting kit-8.Flow cytometry was used to analyze the apoptosis rate,Western blot to determine the levels of apoptosisrelated proteins,and dual luciferase reporter assay combined with RNA-binding protein immunoprecipitation to analyze the relationship between OIP5-AS1 and miR-137.RESULTS OIP5-AS1 was up-regulated in CC tissues and cells,while miR-137 was downregulated in CC tissues and cells.OIP5-AS1 was inversely correlated with miR-137(P<0.001).Silencing OIP5-AS1 expression significantly hindered the proliferation,invasion and migration abilities of CC cells and markedly increased the apoptosis rate.Up-regulation of miR-137 expression also suppressed these abilities in CC cells and increased the apoptosis rate.Moreover,silencing OIP5-AS1 and up-regulating miR-137 expression significantly intensified growth inhibition of drug-resistant CC cells and improved the sensitivity of CC cells to LOHP.OIP5-AS1 targetedly inhibited miR-137 expression,and silencing OIP5-AS1 reversed the resistance of CC cells to L-OHP by promoting the expression of miR-137.CONCLUSION Highly expressed in CC,OIP5-AS1 can affect the biological behavior of CC cells,and can also regulate the resistance of CC cells to L-OHP by mediating miR-137 expression.
基金National Natural Science Foundation of China,No.81974372.
文摘BACKGROUND Previous studies have suggested that long non-coding RNAs(lncRNA)TP73-AS1 is significantly upregulated in several cancers.However,the biological role and clinical significance of TP73-AS1 in pancreatic cancer(PC)remain unclear.AIM To investigate the role of TP73-AS1 in the growth and metastasis of PC.METHODS The expression of lncRNA TP73-AS1,miR-128-3p,and GOLM1 in PC tissues and cells was detected by quantitative real-time polymerase chain reaction.The bioinformatics prediction software ENCORI was used to predict the putative binding sites of miR-128-3p.The regulatory roles of TP73-AS1 and miR-128-3p in cell proliferation,migration,and invasion abilities were verified by Cell Counting Kit-8,wound-healing,and transwell assays,as well as flow cytometry and Western blot analysis.The interactions among TP73-AS1,miR-128-3p,and GOLM1 were explored by bioinformatics prediction,luciferase assay,and Western blot.RESULTS The expression of TP73-AS1 and miRNA-128-3p was dysregulated in PC tissues and cells.High TP73-AS1 expression was correlated with a poor prognosis.TP73-AS1 silencing inhibited PC cell proliferation,migration,and invasion in vitro as well as suppressed tumor growth in vivo.Mechanistically,TP73-AS1 was validated to promote PC progression through GOLM1 upregulation by competitively binding to miR-128-3p.CONCLUSION Our results demonstrated that TP73-AS1 promotes PC progression by regulating the miR-128-3p/GOLM1 axis,which might provide a potential treatment strategy for patients with PC.
基金supported by grants from the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX17_1301 to E.Z.)the National Natural Science Foundation of China (81730066 to D.M.).
文摘Gastric cancer is one of the most common malignant gastrointestinal tumors whose morbidity and mortality account for the second and third place respectively in malignant tumors in China.As an important participant in tumor biology,the abnormal expression of long non-coding RNA(lncRNAs)in cancer cells is closely related to the occurrence and development of tumors and plays the role of oncogenes or tumor suppressor genes.In this study,we identified a novel lncRNA NFIA antisense RNA 1(NFIA-AS1)and explored its role and clinical significance in gastric cancer.Real-time quantitative PCR was performed to detect the expression of NFIA-AS1 in tumor tissues and corresponding normal tissues from 42 pairs of gastric cancer samples.The lower expression of NFIA-AS1 was significantly associated with larger tumor size,lower histological grade,and advanced TNM stage.Kaplan-meier analysis showed that NFIA-AS1 expression could be used as an independent predictor of overall survival.We also demonstrated that overexpression of NFIA-AS1 significantly inhibited the proliferation of gastric cancer cells through affecting p16 levels.In conclusion,our results suggest that the lncRNA NFIA-AS1 may play the role of tumor suppressor gene,and serve as a biomarker for prognosis or progression of gastric cancer.
文摘Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides mostly transcribed by RNA which do not encode proteins. Previously, lncRNAs were considered transcriptional byproducts called “junk DNA” with no biological functions. There are many studies conducted on lncRNAs showing they are actively involved in regulation of epigenetic, transcriptional, and post-transcriptional events. Expressions of lncRNAs are more different in many malignant tumors than in benign tumors and normal tissue. Aberration of lncRNAs is responsible to promote or suppress tumorigenesis and cancer progression. Under different circumstances, lncRNAs exhibit their roles in carcinogenesis such as MALAT1 is responsible for intervening mRNA instability, HOTAIR, MALAT1, ANRIL, PVT1 links with miRNA and histonemodifying complexes, MEG3 associates with miRNA, CCAT2, MEG3, GAS5, UCA1 allies with c-Myc or P53 causing suppression of tumor or oncogenesis. Abnormal expressions of lncRNAs are noticed in gynecological cancers, such as cervical cancer, ovarian cancer, and endometrial cancer. Identification of cervical cancer associated lncRNAs is necessary to understand the molecular biogenesis of cancers. In this review, we summarized the foundation and function of the lncRNAs in terms of tumor progression, invasion, prognosis, apoptosis, metastasis, and chemo-resistance. This review will provide references to determine the clinical applications of lncRNAs as ideal diagnostic biomarkers or therapeutic targets in cervical cancers.
基金This work was supported by grants from Beijing Municipal Natural Science Foundation(No.7184196)Beijing Municipal Administration of Hospitals’Ascent Plan(No.DFL20180202)+1 种基金Capital Health Development Research Project(No.Shoufa-2018-2-2054)Beijing Natural Science Foundation Program and Scientific Research Key Program of Beijing Municipal Commission of Education(No.KZ201910025034)。
文摘Background:Long non-coding RNAs(lncRNAs)play key roles in human cancers.In our previous study,we demonstrated that lncRNA FKBP prolyl isomerase 9 pseudogene 1(FKBP9P1)was highly expressed in head and neck squamous cell cancer(HNSCC)tissues.However,its functional significance remains poorly understood.In the present study,we identify the role and potential molecular biologic mechanisms of FKBP9P1 in HNSCC.Methods:Quantitative real-time polymerase chain reaction was used to detect the expression of FKBP9P1 in HNSCC tissues,matched adjacent normal tissues,human HNSCC cells(FaDu,Cal-27,SCC4,and SCC9),and human immortalized keratinocytes cell HaCaT(normal control).Cal-27 and SCC9 cells were transfected with sh-FKBP9P1-1,sh-FKBP9P1-2,and normal control(sh-NC)lentivirus.Cell counting kit-8 assay,colony formation assay,wound healing assay,and trans-well assay were used to explore the biologic function of FKBP9P1 in HNSCC cells.Furthermore,western blotting was used to determine the mechanism of FKBP9P1 in HNSCC progression.Chi-squared test was performed to assess the clinical significance among FKBP9P1 high-expression and low-expression groups.Survival analyses were performed using the Kaplan-Meier method and assessed using the log-rank test.The comparison between two groups was analyzed by Student t test,and comparisons among multiple samples were performed by one-way analysis of variance and a Bonferroni post hoc test.Results:FKBP9P1 expression was significantly up-regulated in HNSCC tissues(tumor vs.normal,1.914 vs.0.957,t=7.746,P<0.001)and cell lines(P<0.01 in all HNSCC cell lines).Besides,the median FKBP9P1 expression of HNSCC tissues(1.677)was considered as the threshold.High FKBP9P1 level was correlated with advanced T stage(P=0.022),advanced N stage(P=0.036),advanced clinical stage(P=0.018),and poor prognosis of HNSCC patients(overall survival,P=0.002 and disease-free survival,P<0.001).Knockdown of FKBP9P1 led to marked repression in proliferation,migration,and invasion of HNSCC cells in vitro(P all<0.01).Mechanistically,silencing FKBP9P1 was observed to restrain the PI3K/AKT signaling pathway.Conclusions:Silencing lncRNA FKBP9P1 represses HNSCC progression and inhibits PI3K/AKT(phosphatidylinositol 3 kinase/AKT Serine/Threonine Kinase)signaling in vitro.Therefore,FKBP9P1 could be a potential new target for the diagnosis and treatment of HNSCC patients.
文摘Background:Long non-coding RNA(lncRNA)actin filament-associated protein 1 antisense RNA 1(AFAP1-AS1)functions as a competing endogenous RNA to regulate target genes expression by sponging microRNAs(miRs)to play cancer-promoting roles in cancer stem cells.However,the regulatory mechanism of AFAP1-AS1 in cervical cancer(CC)stem cells is unknown.The present study aimed to provide a new therapeutic target for the clinical treatment of CC.Methods:Hyaluronic acid receptor cluster of differentiation 44 variant exon 6(CD44v6)(+)CC cells were isolated by flow cytometry(FCM).Small interfering RNAs of AFAP1-AS1(siAFAP1-AS1)were transfected into the(CD44v6)(+)cells.The levels of AFAP1-AS1 were measured by quantitative real-time PCR(qRT-PCR).Sphere formation assay,cell cycle analysis,and Western blotting were used to detect the effect of siAFAP1-AS1.RNA pull-down and luciferase reporter assay were used to verify the relationship between miR-27b-3p and AFAP1-AS1 or vascular endothelial growth factor(VEGF)-C.Results:CD44v6(+)CCcells had remarkable stemness and a high level ofAFAP1-AS1.However,AFAP1-AS1knockdownwithsiAFAP1-AS1suppressed the cell cycle transitionofG(1)/S phase and inhibited self-renewal ofCD44v6(+)CCcells,the levels of the stemnessmarkers octamer-binding transcription factor 4(OCT4),osteopontin(OPN),and cluster of differentiation 133(CD133),and the epithelialmesenchymal transition(EMT)-related proteins Twist1,matrix metalloprotease(MMP)-9,and VEGF-C.In the mechanism study,miR-27b-3p/VEGF-C signaling was demonstrated to be a key downstream of AFAP1-AS1 in the CD44v6(+)CC cells.Conclusions:LncRNA AFAP1-AS1 knockdown inhibits the CC cell stemness by upregulating miR-27b-3p to suppress VEGF-C.
