Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected indi...Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.展开更多
Activating V600E in v-Raf murine sarcoma viral oncogene homolog B(BRAF)is a common driver mutation in cancers of multiple tissue origins,including melanoma and glioma.BRAF^(V600E) has also been implicated in neurodege...Activating V600E in v-Raf murine sarcoma viral oncogene homolog B(BRAF)is a common driver mutation in cancers of multiple tissue origins,including melanoma and glioma.BRAF^(V600E) has also been implicated in neurodegeneration.The present study aims to characterize BRAF^(V600E) during cell death and proliferation of three major cell types of the central nervous system:neurons,astrocytes,and microglia.Multiple primary cultures(primary cortical mixed culture)and cell lines of glial cells(BV2)and neurons(SH-SY5Y)were employed.BRAF^(V600E) and BRAF^(WT) expression was mediated by lentivirus or retrovirus.Blockage of downstream effectors(extracellular signal-regulated kinase 1/2 and JNK1/2)were achieved by siRNA.In astrocytes and microglia,BRAF^(V600E) induces cell proliferation,and the proliferative effect in microglia is mediated by activated extracellular signal-regulated kinase,but not c-Jun N-terminal kinase.Conditioned medium from BRAF^(V600E)-expressing microglia induced neuronal death.In neuronal cells,BRAF^(V600E) directly induces neuronal death,through c-Jun N-terminal kinase but not extracellular signal-regulated kinase.We further show that BRAF-related genes are enriched in pathways in patients with Parkinson’s disease.Our study identifies distinct consequences mediated by distinct downstream effectors in dividing glial cells and in neurons following the same BRAF mutational activation and a causal link between BRAF-activated microglia and neuronal cell death that does not require physical proximity.It provides insight into a possibly important role of BRAF in neurodegeneration as a result of either dysregulated BRAF in neurons or its impact on glial cells.展开更多
Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of ...Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.展开更多
Objective\ To understand the transcription of BamHI L DNA fragment from genome of strong virulent GA strain of Marek′s disease herpesvirus (MDV) in lymphoblastoid tumor tissue induced by oncogenic strain Beijing 1 (a...Objective\ To understand the transcription of BamHI L DNA fragment from genome of strong virulent GA strain of Marek′s disease herpesvirus (MDV) in lymphoblastoid tumor tissue induced by oncogenic strain Beijing 1 (a specific local strain in China) of MDV. Methods\ Two oligonucleotide primers were synthesized according to the reported sequence of \%meq\% gene an ideal oncogenic candidate and our previously determined sequence of BamHI L fragment of Marek′s disease herpesvirus (MDV), respectively. Reverse transcriptase PCR(RT PCR) assay was performed by using these primers and the mRNA as a template which was isolated from visceral lymphoblastoid tumors obtained from chickens artificially infected with strain Beijing 1 of oncogenic MDV. Southern blot molecular hybridization was further carried out to detect the product of RT PCR with digoxigenin labeled nucleotide probe from BamHI I2 and L fragment in the gene library of MDV strain GA, respectively. Results\ Two probes could simultaneously hybridize this cDNA amplified by RT PCR with a length of about 730 bp. Conclusion\ It is suggested that \%meq\% transcription could extend from the right hand end of BamHI I2 to the adjacent BamHI L, and the BamHI L region was likely to be transcribed in MDV induced lymphoblastoid tumors.展开更多
Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEG...Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS(KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.展开更多
BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory diseases.AIM To assess the status ...BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory diseases.AIM To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development.METHODS Flow cytometry assay,immunohistochemistry,and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer.Prior to cell suspension culture,ELISA was carried out to measure the production of IL-6,IL-1β,IL-23,CXCL12,and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer.In addition,multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.RESULTS Compared with normal tissues,Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients.Cancer cells produced a greater amount of IL-6,IL-1β,and IL-23,which in turn promoted Tc17 cell polarization.Unlike the traditional cytotoxic CD8^+T cells,Tc17 cells secreted IL-17,which subsequently promoted CXCL12 expression in tumor cells,eventually enhancing the proliferation and migration of tumor cells.Thus,the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer.CONCLUSION Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer.We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.展开更多
Objective: To find out the incidence of high-risk HPV infections on climacteric women within our area of influence;and to typify HPV genotypes on women with normal cytology that come to our hospitalary unit of menopau...Objective: To find out the incidence of high-risk HPV infections on climacteric women within our area of influence;and to typify HPV genotypes on women with normal cytology that come to our hospitalary unit of menopausia. Material and Method: Cross-sectional study;with a random sample of 140 cases of climacteric women of ≥50 years of age, with normal Pap smears for the last 12 months. HPV determination was carried out by PCR for screening, and by hybrid capture for genotype typification. Results: The percentage of climacteric women who are carriers of oncogenic HPV and a normal Pap smear was of 11.43% (16/140 cases). The genotype found most frequently was HPV-16, followed by HPV-58, 51 and 18. Conclusions: We found a high prevalence of women who were carriers of oncogenic HPV in climacteric women with normal Pap smears (latent infections) in our health region. We consider that cervical cancer screening, either by PCR or conventional Pap smear, should not be minimized or ignored from 50 years of age onwards.展开更多
BACKGROUND Oncogenic osteomalacia caused by phosphaturic mesenchymal tumors is very difficult to detect.We report a case of tumor-induced osteomalacia caused by a phosphaturic mesenchymal tumor of the left femur in a ...BACKGROUND Oncogenic osteomalacia caused by phosphaturic mesenchymal tumors is very difficult to detect.We report a case of tumor-induced osteomalacia caused by a phosphaturic mesenchymal tumor of the left femur in a middle-aged woman after medical imaging and biopsy.CASE SUMMARY A 57-year-old woman presented with progressive bone pain for five years.She was diagnosed with hypophosphatemic osteomalacia,as her laboratory data showed low serum phosphorus and low serum calcium.Her knee joint radiography revealed an osteolytic lesion of the left femur.A computed tomography scan showed mixed density shadows in the left femur.Magnetic resonance imaging of the left femur showed the presence of an oval area with a hypointense signal in T1-weighted magnetic resonance imaging(MRI)and highlow mixed signal in T2-weighted MRI.Biopsy samples revealed the presence of short spindle cells,vascularization,and characteristics of phosphaturic mesenchymal tumors.Tumor resection was performed,and the clinical presentations and laboratory abnormalities were reversed.CONCLUSION Diagnosis of oncogenic osteomalacia is difficult due to the varieties and localization of source tumors and absence of pathognomonic biomedical signs.Our case highlights the importance of a combination of medical imaging and biopsy in the diagnosis of oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor.展开更多
A total of 531 sexually active female populations from Manipur (north-eastern India), was chosen for this study. Out of 531 females from Manipur, 111 (20.9%) were HIV positive and 420 were HIV negative (79%). PCR ampl...A total of 531 sexually active female populations from Manipur (north-eastern India), was chosen for this study. Out of 531 females from Manipur, 111 (20.9%) were HIV positive and 420 were HIV negative (79%). PCR amplification of the MY region of the HPV L1 gene using consensus MY09/11 primer showed 3.7% positivity in Manipur. Interestingly HPV infection among the HIV infected population from Manipur was found to be higher (9%) compared to the non HIV infected population from Manipur (3.7%). Further, single PCR for detecting the 16/18 genotypes and multiplex PCR for the other high risk groups showed equal prevalence of 16 and 18 and other high risk groups (1.3% each) in Manipur. This result was further confirmed by the sequencing and phylogenetic analysis. Thus, our study showed fairly high HPV prevalence rate among the HIV infected population compared to the non HIV cases in Manipur and also equal prevalence of 16/18 genotypes with other high risk groups. According to our knowledge this is the first kind of a genotypic study among the HPV-HIV co-infected population from northeastern states of India.展开更多
The Intrinsic structural disorder (ISD) of native EWS and its fusion oncogenic proteins, including EWS/FliI, EWS/ATF1 and EWS/ZSG, was estimated by different Predictors. The ISD difference between the wild type and th...The Intrinsic structural disorder (ISD) of native EWS and its fusion oncogenic proteins, including EWS/FliI, EWS/ATF1 and EWS/ZSG, was estimated by different Predictors. The ISD difference between the wild type and the oncogenic fusions found in the CTD is due to the fusion partner, usually a transcription factor (TF). A disordered region was found in the sequence (AA 132 - 156) of the NTD (EAD) of EWS, consisting of the longest region free of Y motifs. The IQ domain (AA 258 - 280), a Y-free region, flanked by two Y-boxes, is also disordered by all used Predictors. The EWS functional regions RGG1, RGG2 and RGG3 are predominantly disordered. A strong dependence was found between the structure of EWS protein and its oncogenic fusions, and their estimated ISD. The oncogenic function of the fusions is related to a decreased ISD in the CTD, due to the fused TF. The Predictors shown that the different isoforms have similar profiles, shifted with some amino acids, due to the translocations. On the bases of the prediction results, an analysis was made of the EWS sequence and its functional regions with increased ISD to make a relationship sequence-disorder-function that could be helpful in the design of antitumor agents against the corresponding malignances.展开更多
Oncogenic osteomalacia (OOM) is an uncommon metabolic and bone disease caused by fibroblast growth factor 23 (FGF23), a phosphaturic factor produced by phosphaturic mesenchymal tumors (mixed connective tissue variant,...Oncogenic osteomalacia (OOM) is an uncommon metabolic and bone disease caused by fibroblast growth factor 23 (FGF23), a phosphaturic factor produced by phosphaturic mesenchymal tumors (mixed connective tissue variant, PMTMCTV) characterized by phosphate leakage from kidneys and subsequent hypophosphatemia. In this paper, we present the case of a patient, 42-year-old woman affected by left side limp and pain involving lumbar spine, pelvis and hip joints, referred to the Rheumatology Department of our Hospital for the treatment of a suspected sero-negative spondilo-arthritis. During hospitalization patient began an immuno-suppressive therapy with TNF-alpha inhibitors associated with Pamidornate, Indometacin, Esomeprazole and vitamin D3. Nevertheless pain did not decrease and a new examination found a worst hypophosphatemia (1 mg/dl) with normal Ca and PTH’s plasma values. During the same check-up a painful bulge on the anterior part of the right knee was observed and the Magnetic Resonance Imaging scan revealed an ovular solid lesion in the soft tissue closed to the upper part of the patella. Histological analysis identified the lesion as a PMTMCTV. After surgical removal patient got complete recovery. We will discuss about diagnostic evaluation, differential diagnosis and treatment.展开更多
A well-known tumor suppressor, p21, acts parado-xically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinoge...A well-known tumor suppressor, p21, acts parado-xically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma(HCC) therapy. Chromosome region maintenance 1(CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention.展开更多
The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is ove...The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.展开更多
Lung cancer,of which non-small lung cancer is the most common subtype,represents the leading cause of cancer related-death worldwide.It is now recognized that a significant proportion of these patients present alterat...Lung cancer,of which non-small lung cancer is the most common subtype,represents the leading cause of cancer related-death worldwide.It is now recognized that a significant proportion of these patients present alterations in certain genes that drive oncogenesis.In recent years,more of these so-called oncogenic drivers have been identified,and a better understanding of their biology has allowed the development new targeted agents.This review aims to provide an update about the current landscape of driver mutation in non-smallcell lung cancer.Alterations in Kirsten rat sarcoma,epidermal growth factor receptor,MET,anaplastic lymphoma kinase,c-ROS oncogene 1,v-raf murine sarcoma viral oncogene homolog B,neurotrophic receptor tyrosine kinase,human epidermal growth factor 2,neuregulin-1 and rearranged during transfection are discussed,as well as agents targeting these alterations.Current standards of treatment as well as promising future strategies are presented.Currently,more than fifteen targeted agents are food and Drug administration-approved for seven oncogenic drivers in non-small-cell lung cancer,highlighting the importance of actively searching for these mutations.Continuous and future efforts made in defining the biology of each of these alterations will help to elucidate their respective resistance mechanisms,and to define the best treatment strategy and therapeutic sequence.展开更多
With the support of the National Natural Science Foundation of China and the Chinese Academy of Sciences,the laboratory led by Yang CaiGuang(杨财广)from Shanghai Institute of Materia Medica,Chinese Academy of Sciences...With the support of the National Natural Science Foundation of China and the Chinese Academy of Sciences,the laboratory led by Yang CaiGuang(杨财广)from Shanghai Institute of Materia Medica,Chinese Academy of Sciences,has identified a potential therapeutic small molecule for treating the acute myeloid leukemia(AML)by targeting the oncogenic RNA demethylase FTO,which was published in Figure Schematic diagram of small-molecular targeting of the oncogenic FTO demethylase.Cancer Cell(2019,35:677—691).展开更多
Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a...Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.展开更多
The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate...The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.展开更多
BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has sho...BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.展开更多
文摘Background:Oral squamous cell carcinoma(OSCC)represents a prevalent malignancy in the oral and maxillofacial area,having a considerable negative impact on both the quality of life and overall survival of affected individuals.Our research endeavors to leverage bioinformatic approaches to elucidate oncogenic signaling pathways,with the ultimate goal of gaining deeper insights into the molecular underpinnings of OSCC pathogenesis,and thus laying the groundwork for the development of more effective therapeutic and preventive strategies.Methods:Differential expression analysis was performed on mRNA data from tumor and normal tissue groups to identify genes associated with OSCC,using The Cancer Genome Atlas database.Predictions of oncogenic signaling pathways linked to differentially expressedmRNAs were made,and these results were presented visually using R software,using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichments.Results:GO and KEGG analyses of 2938 differentially expressed genes in OSCC highlighted their significant involvement in various biological processes.Notably,these processes were related to the extracellular matrix,structural organization,connective tissue development,and cell cycle regulation.Conclusions:The comprehensive exploration of gene expression patterns provides valuable insights into potential oncogenic mechanisms in OSCC.
基金supported by the National Institutes of Health,No. R01NS102735 (to XC)the National Natural Science Foundation of China,No. 82073072 (to XC)+1 种基金the Michael J. Fox Foundation for Parkinson’s Research (MJFF)the Aligning Science Across Parkinson’s Initiative (ASAP),No. ASAP-000312 (to XC)
文摘Activating V600E in v-Raf murine sarcoma viral oncogene homolog B(BRAF)is a common driver mutation in cancers of multiple tissue origins,including melanoma and glioma.BRAF^(V600E) has also been implicated in neurodegeneration.The present study aims to characterize BRAF^(V600E) during cell death and proliferation of three major cell types of the central nervous system:neurons,astrocytes,and microglia.Multiple primary cultures(primary cortical mixed culture)and cell lines of glial cells(BV2)and neurons(SH-SY5Y)were employed.BRAF^(V600E) and BRAF^(WT) expression was mediated by lentivirus or retrovirus.Blockage of downstream effectors(extracellular signal-regulated kinase 1/2 and JNK1/2)were achieved by siRNA.In astrocytes and microglia,BRAF^(V600E) induces cell proliferation,and the proliferative effect in microglia is mediated by activated extracellular signal-regulated kinase,but not c-Jun N-terminal kinase.Conditioned medium from BRAF^(V600E)-expressing microglia induced neuronal death.In neuronal cells,BRAF^(V600E) directly induces neuronal death,through c-Jun N-terminal kinase but not extracellular signal-regulated kinase.We further show that BRAF-related genes are enriched in pathways in patients with Parkinson’s disease.Our study identifies distinct consequences mediated by distinct downstream effectors in dividing glial cells and in neurons following the same BRAF mutational activation and a causal link between BRAF-activated microglia and neuronal cell death that does not require physical proximity.It provides insight into a possibly important role of BRAF in neurodegeneration as a result of either dysregulated BRAF in neurons or its impact on glial cells.
文摘Hepatocellular carcinoma(HCC) is one of the most common causes of cancer-related death worldwide. Chronic infection of hepatitis B virus(HBV) and/or hepatitis C virus(HCV) is a major risk factor in the development of the HCC, independently from excessive alcohol abuse and metabolic disease. Since the biology of HBV and HCV is different, their oncogenic effect may go through different mechanisms, direct and/or indirect. Viral hepatitis infection is associated with cellular inflammation, oxidative stress, DNA damage, that may lead to subsequent hepatic injuries such as chronic hepatitis, fibrosis, cirrhosis, and finally HCC. Direct oncogenic properties of these viruses are related with their genotypic characteristics and the ability of viral proteins to interact with host proteins, thus altering the molecular pathways balance of the cells. In addition, the integration of HBV DNA, especially the gene S and X, in a particular site of the host genome can disrupt chromosomal stability and may activate various oncogenic mechanisms, including those in hematopoietic cells. Recently, several studies also had demonstrated that viral hepatitis could trigger the population of hepatic cancer stem cells. This review summarize available pre-clinical and clinical data in literature regarding oncogenic properties of HBV and HCV in the early initiation of HCC.
文摘Objective\ To understand the transcription of BamHI L DNA fragment from genome of strong virulent GA strain of Marek′s disease herpesvirus (MDV) in lymphoblastoid tumor tissue induced by oncogenic strain Beijing 1 (a specific local strain in China) of MDV. Methods\ Two oligonucleotide primers were synthesized according to the reported sequence of \%meq\% gene an ideal oncogenic candidate and our previously determined sequence of BamHI L fragment of Marek′s disease herpesvirus (MDV), respectively. Reverse transcriptase PCR(RT PCR) assay was performed by using these primers and the mRNA as a template which was isolated from visceral lymphoblastoid tumors obtained from chickens artificially infected with strain Beijing 1 of oncogenic MDV. Southern blot molecular hybridization was further carried out to detect the product of RT PCR with digoxigenin labeled nucleotide probe from BamHI I2 and L fragment in the gene library of MDV strain GA, respectively. Results\ Two probes could simultaneously hybridize this cDNA amplified by RT PCR with a length of about 730 bp. Conclusion\ It is suggested that \%meq\% transcription could extend from the right hand end of BamHI I2 to the adjacent BamHI L, and the BamHI L region was likely to be transcribed in MDV induced lymphoblastoid tumors.
文摘Epidermal growth factor receptor(EGFR) has been an attractive target for treatment of epithelial cancers, including colorectal cancer(CRC). Evidence from clinical trials indicates that cetuximab and panitumumab(antiEGFR monoclonal antibodies) have clinical activity in patients with metastatic CRC. The discovery of intrinsic EGFR blockade resistance in Kirsten RAS(KRAS)-mutant patients led to the restriction of anti-EGFR antibodies to KRAS wild-type patients by Food and Drug Administration and European Medicine Agency. Studies have since focused on the evaluation of biomarkers to identify appropriate patient populations that may benefit from EGFR blockade. Accumulating evidence suggests that patients with mutations in EGFR downstream signaling pathways including KRAS, BRAF, PIK3CA and PTEN could be intrinsically resistant to EGFR blockade. Recent whole genome studies also suggest that dynamic alterations in signaling pathways downstream of EGFR leads to distinct oncogenic signatures and subclones which might have some impact on emerging resistance in KRAS wild-type patients. While anti-EGFR monoclonal antibodies have a clear potential in the management of a subset of patients with metastatic CRC, further studies are warranted to uncover exact mechanisms related to acquired resistance to EGFR blockade.
文摘BACKGROUND As one of the subsets of CD8+T cells,Tc17 cells have recently been identified and are characterized by the secretion of interleukin(IL)-17,which is related to inflammatory diseases.AIM To assess the status of Tc17 cells in cervical cancer and investigate the biological function of Tc17 cells in cervical cancer development.METHODS Flow cytometry assay,immunohistochemistry,and immunofluorescence were performed to detect the levels and phenotype of Tc17 cells in blood and tumor samples from patients with cervical cancer.Prior to cell suspension culture,ELISA was carried out to measure the production of IL-6,IL-1β,IL-23,CXCL12,and IL-17 in tumor tissue supernatant and co-cultured supernatant of patients with cervical cancer.In addition,multivariate analysis was performed to identify factors associated with overall survival using the Cox proportional hazards model.RESULTS Compared with normal tissues,Tc17 cells specifically accumulated in tumor tissues of cervical cancer patients.Cancer cells produced a greater amount of IL-6,IL-1β,and IL-23,which in turn promoted Tc17 cell polarization.Unlike the traditional cytotoxic CD8^+T cells,Tc17 cells secreted IL-17,which subsequently promoted CXCL12 expression in tumor cells,eventually enhancing the proliferation and migration of tumor cells.Thus,the ratio of tumor-infiltrating Tc17 cells was highly correlated with poor clinical outcome in patients with cervical cancer.CONCLUSION Our data identified the oncogenic role of Tc17 cells in the development of cervical cancer.We propose that the ratio of Tc17 cells may be a useful index in the prognosis of patients with cervical cancer.
文摘Objective: To find out the incidence of high-risk HPV infections on climacteric women within our area of influence;and to typify HPV genotypes on women with normal cytology that come to our hospitalary unit of menopausia. Material and Method: Cross-sectional study;with a random sample of 140 cases of climacteric women of ≥50 years of age, with normal Pap smears for the last 12 months. HPV determination was carried out by PCR for screening, and by hybrid capture for genotype typification. Results: The percentage of climacteric women who are carriers of oncogenic HPV and a normal Pap smear was of 11.43% (16/140 cases). The genotype found most frequently was HPV-16, followed by HPV-58, 51 and 18. Conclusions: We found a high prevalence of women who were carriers of oncogenic HPV in climacteric women with normal Pap smears (latent infections) in our health region. We consider that cervical cancer screening, either by PCR or conventional Pap smear, should not be minimized or ignored from 50 years of age onwards.
基金Supported by Research Fund of Hangzhou Normal University Affiliated Hospital
文摘BACKGROUND Oncogenic osteomalacia caused by phosphaturic mesenchymal tumors is very difficult to detect.We report a case of tumor-induced osteomalacia caused by a phosphaturic mesenchymal tumor of the left femur in a middle-aged woman after medical imaging and biopsy.CASE SUMMARY A 57-year-old woman presented with progressive bone pain for five years.She was diagnosed with hypophosphatemic osteomalacia,as her laboratory data showed low serum phosphorus and low serum calcium.Her knee joint radiography revealed an osteolytic lesion of the left femur.A computed tomography scan showed mixed density shadows in the left femur.Magnetic resonance imaging of the left femur showed the presence of an oval area with a hypointense signal in T1-weighted magnetic resonance imaging(MRI)and highlow mixed signal in T2-weighted MRI.Biopsy samples revealed the presence of short spindle cells,vascularization,and characteristics of phosphaturic mesenchymal tumors.Tumor resection was performed,and the clinical presentations and laboratory abnormalities were reversed.CONCLUSION Diagnosis of oncogenic osteomalacia is difficult due to the varieties and localization of source tumors and absence of pathognomonic biomedical signs.Our case highlights the importance of a combination of medical imaging and biopsy in the diagnosis of oncogenic osteomalacia caused by a phosphaturic mesenchymal tumor.
文摘A total of 531 sexually active female populations from Manipur (north-eastern India), was chosen for this study. Out of 531 females from Manipur, 111 (20.9%) were HIV positive and 420 were HIV negative (79%). PCR amplification of the MY region of the HPV L1 gene using consensus MY09/11 primer showed 3.7% positivity in Manipur. Interestingly HPV infection among the HIV infected population from Manipur was found to be higher (9%) compared to the non HIV infected population from Manipur (3.7%). Further, single PCR for detecting the 16/18 genotypes and multiplex PCR for the other high risk groups showed equal prevalence of 16 and 18 and other high risk groups (1.3% each) in Manipur. This result was further confirmed by the sequencing and phylogenetic analysis. Thus, our study showed fairly high HPV prevalence rate among the HIV infected population compared to the non HIV cases in Manipur and also equal prevalence of 16/18 genotypes with other high risk groups. According to our knowledge this is the first kind of a genotypic study among the HPV-HIV co-infected population from northeastern states of India.
文摘The Intrinsic structural disorder (ISD) of native EWS and its fusion oncogenic proteins, including EWS/FliI, EWS/ATF1 and EWS/ZSG, was estimated by different Predictors. The ISD difference between the wild type and the oncogenic fusions found in the CTD is due to the fusion partner, usually a transcription factor (TF). A disordered region was found in the sequence (AA 132 - 156) of the NTD (EAD) of EWS, consisting of the longest region free of Y motifs. The IQ domain (AA 258 - 280), a Y-free region, flanked by two Y-boxes, is also disordered by all used Predictors. The EWS functional regions RGG1, RGG2 and RGG3 are predominantly disordered. A strong dependence was found between the structure of EWS protein and its oncogenic fusions, and their estimated ISD. The oncogenic function of the fusions is related to a decreased ISD in the CTD, due to the fused TF. The Predictors shown that the different isoforms have similar profiles, shifted with some amino acids, due to the translocations. On the bases of the prediction results, an analysis was made of the EWS sequence and its functional regions with increased ISD to make a relationship sequence-disorder-function that could be helpful in the design of antitumor agents against the corresponding malignances.
文摘Oncogenic osteomalacia (OOM) is an uncommon metabolic and bone disease caused by fibroblast growth factor 23 (FGF23), a phosphaturic factor produced by phosphaturic mesenchymal tumors (mixed connective tissue variant, PMTMCTV) characterized by phosphate leakage from kidneys and subsequent hypophosphatemia. In this paper, we present the case of a patient, 42-year-old woman affected by left side limp and pain involving lumbar spine, pelvis and hip joints, referred to the Rheumatology Department of our Hospital for the treatment of a suspected sero-negative spondilo-arthritis. During hospitalization patient began an immuno-suppressive therapy with TNF-alpha inhibitors associated with Pamidornate, Indometacin, Esomeprazole and vitamin D3. Nevertheless pain did not decrease and a new examination found a worst hypophosphatemia (1 mg/dl) with normal Ca and PTH’s plasma values. During the same check-up a painful bulge on the anterior part of the right knee was observed and the Magnetic Resonance Imaging scan revealed an ovular solid lesion in the soft tissue closed to the upper part of the patella. Histological analysis identified the lesion as a PMTMCTV. After surgical removal patient got complete recovery. We will discuss about diagnostic evaluation, differential diagnosis and treatment.
基金Supported by Grant-in-Aid for Scientific Research(C)(22590722 for Ohkoshi S)from the Japan Society for the promotion of Science(JSPS)
文摘A well-known tumor suppressor, p21, acts parado-xically by promoting tumor growth in some cellular conditions. These conflicting functions have been demonstrated in association with the HBx gene and in hepatocarcinogenesis. The molecular behavior of p21 depends on its subcellular localization. Nuclear p21 may inhibit cell proliferation and be proapoptotic, while cytoplasmic p21 may have oncogenic and anti-apoptotic functions. Because most typical tumor suppressive proteins also have different effects according to subcellular localization, elucidating the regulatory mechanisms underlying nucleo-cytoplasmic transport of these proteins would be significant and may lead to a new strategy for anti-hepatocellular carcinoma(HCC) therapy. Chromosome region maintenance 1(CRM1) is a major nuclear export receptor involved in transport of tumor suppressors from nucleus to cytoplasm. Expression of CRM1 is enhanced in a variety of malignancies and in vitro studies have shown the efficacy of specific inhibition of CRM1 against cancer cell lines. Interestingly, interferon may keep p21 in the nucleus; this is one of the mechanisms of its anti-hepatocarcinogenic function. Here we review the oncogenic property of p21, which depends on its subcellular localization, and discuss the rationale underlying a new strategy for HCC treatment and prevention.
文摘The miniature chromosome maintenance(MCM)complex is a group of proteins that are essential for DNA replication licensing and control of cell cycle progression from G1 to S phase.Recent studies suggest that MCM7 is overexpressed and amplified in a variety of human malignancies.MCM7 genome sequence contains a cluster of miRNA that has been shown to downregulate expression of several tumor suppressors including p21,E2F1,BIM and pTEN.The oncogenic potential of MCM7 and its embedded miRNA has been demonstrated vigorously in in vitro experiments and in animal models,and they appear to cooperate in initiation of cancer.MCM7 protein also serves as a critical target for oncogenic signaling pathways such as androgen receptor signaling,or tumor suppressor pathways such as integrinα7 or retinoblastoma signaling.This review analyzes the transforming activity and signaling of MCM7,oncogenic function of miRNA cluster that is embedded in the MCM7 genome,and the potential of gene therapy that targets MCM7.
文摘Lung cancer,of which non-small lung cancer is the most common subtype,represents the leading cause of cancer related-death worldwide.It is now recognized that a significant proportion of these patients present alterations in certain genes that drive oncogenesis.In recent years,more of these so-called oncogenic drivers have been identified,and a better understanding of their biology has allowed the development new targeted agents.This review aims to provide an update about the current landscape of driver mutation in non-smallcell lung cancer.Alterations in Kirsten rat sarcoma,epidermal growth factor receptor,MET,anaplastic lymphoma kinase,c-ROS oncogene 1,v-raf murine sarcoma viral oncogene homolog B,neurotrophic receptor tyrosine kinase,human epidermal growth factor 2,neuregulin-1 and rearranged during transfection are discussed,as well as agents targeting these alterations.Current standards of treatment as well as promising future strategies are presented.Currently,more than fifteen targeted agents are food and Drug administration-approved for seven oncogenic drivers in non-small-cell lung cancer,highlighting the importance of actively searching for these mutations.Continuous and future efforts made in defining the biology of each of these alterations will help to elucidate their respective resistance mechanisms,and to define the best treatment strategy and therapeutic sequence.
文摘With the support of the National Natural Science Foundation of China and the Chinese Academy of Sciences,the laboratory led by Yang CaiGuang(杨财广)from Shanghai Institute of Materia Medica,Chinese Academy of Sciences,has identified a potential therapeutic small molecule for treating the acute myeloid leukemia(AML)by targeting the oncogenic RNA demethylase FTO,which was published in Figure Schematic diagram of small-molecular targeting of the oncogenic FTO demethylase.Cancer Cell(2019,35:677—691).
基金This work was supported by the Basic Research Program of Yunnan Province-Joint Project of Kunming Medical University No.202101AY070001−169.
文摘Background:Lung adenocarcinoma is a very pervasive histological form of lung cancers,and inhibiting metastasis is crucial for effective treatment.In this investigation,we explored the functional interaction of miR-30a-5p and the putative transcription factor 2 of the homeodomain(PHTF2)in dictating the aggressiveness and metastasis of lung adenocarcinoma.Method:We collected clinical samples to evaluate the expression patterns of miR-30a-5p and PHTF2 in lung adenocarcinoma along with normal tissues.Cellular experiments including cell count kit(CCK)-8 growth assay,apoptosis analysis,migration and invasion examinations were performed to assess the aggressiveness of lung adenocarcinoma cells.Furthermore,we examined tumorigenesis and metastasis in a nude mouse model.Results:MiR-30a-5p exhibited downregulation pattern in lung adenocarcinoma samples.Transfection of miR-30a-5p mimic in lung adenocarcinoma cells resulted in the suppression of malignant characteristics.Notably,the administration of miR-30a-5p mimic also curbed tumorigenesis and metastasis of lung adenocarcinoma cells in animal model.Moreover,PHTF2 was found to be a molecular target of miR-30a-5p.Upregulating PHTF2 counteracted the tumor-suppressive effect of the miR-30a-5p mimic.Conclusion:miR-30a-5p functions as a tumor-suppressive molecule while PHTF2 acts as an oncogenic factor in the development and metastasis of lung adenocarcinoma.Therefore,targeting miR-30a-5p and PHTF2 could be developed into a promising therapeutic approach for inhibiting metastasis in lung adenocarcinoma.
文摘The global incidence of lung cancer is marked by a considerably elevated mortality rate.MicroRNAs(miRNAs)exert pivotal influence in the intricate orchestration of gene regulation,and their dysregulation can precipitate dire consequences,notably cancer.Within this context,miRNAs encapsulated in exosomes manifest a diversified impact on the landscape of lung cancer,wherein their actions may either foster angiogenesis,cell proliferation,and metastasis,or counteract these processes.This comprehensive review article discerns potential targets for the prospective development of therapeutic agents tailored for lung cancer.Tumor-suppressive miRNAs,such as miR-204,miR-192,miR-30a,miR-34a,miR-34b,miR-203,and miR-212,exhibit heightened expression and demonstrate the capacity to inhibit cellular proliferation and invasiveness.Conversely,the deleterious effects of tumor-promoting miRNAs like miR-21,miR-106a,miR-155,miR-205,and miR-210 can be attenuated through the application of their respective inhibitors.Distinct miRNAs selectively target various oncogenes,including NUAK Family Kinase 1(NUAK1),Snail Family Transcriptional Repressor 1(Snai1),Astrocyte elevated gene-1(AEG-1),Vimentin,Proliferation and apoptosis adaptor protein 15(PEA-15/PED),Hypoxia-inducible factor 1-alpha(HIF1),as well as tumor suppressor genes such as phosphatase and tensin homolog(PTEN),Suppressor of cytokine signaling 1(SOCS1),Tumor protein P53 binding protein 1(TP53BP1),and PH Domain and Leucine Rich Repeat Protein Phosphatase 2(PHLP22).This investigative approach proves invaluable in elucidating the specific miRNAs implicated in the deregulation of crucial genes pivotal to the pathogenesis of cancer.
基金Supported by 2020 Guangxi Zhuang Autonomous Region Health Care Commission Self-Financing Research Projects,No.Z202000962023 Guangxi University Young and Middle-Aged Teachers’Basic Research Ability Improvement Project,No.2023KY0091+1 种基金National Natural Science Foundation of China,No.82260241the Natural Science Foundation of Guangxi Province,No.2015GXNSFAA139171 and No.2020GXNSFAA259053.
文摘BACKGROUND Alzheimer’s disease(AD)is a neurodegenerative condition characterized by oxidative stress and neuroinflammation.Tanshinone ⅡA(Tan-ⅡA),a bioactive compound isolated from Salvia miltiorrhiza plants,has shown potential neuroprotective effects;however,the mechanisms underlying such a function remain unclear.AIM To investigate potential Tan-ⅡA neuroprotective effects in AD and to elucidate their underlying mechanisms.METHODS Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology.To assess changes in oxidative stress and neuroinflammation,we performed enzyme-linked immunosorbent assay and western blotting.Additionally,the effect of Tan-ⅡA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.Genetic changes related to the long non-coding RNA(lncRNA)nuclear-enriched abundant transcript 1(NEAT1)/microRNA(miRNA,miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction.RESULTS In vivo,Tan-ⅡA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice.In vitro experiments showed that Tan-ⅡA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability,apoptosis,oxidative stress,and neuroinflammation.In this process,the lncRNA NEAT1-a potential therapeutic target-is highly expressed in AD mice and downregulated via Tan-ⅡA treatment.Mechanistically,NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p,which activates nuclear factor kappa-B(NF-κB)signaling,leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein,which exacerbates AD.Tan-ⅡA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling.CONCLUSION This study demonstrates that Tan-ⅡA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway,serving as a foundation for the development of innovative approaches for AD therapy.
