目的:采用Meta分析评价TERT启动子突变和膀胱癌临床病理特征的关系。方法:检索Cochrane Library、Embase、PubMed、Web of Science、万方全文数据库、中国知网数据库,搜索与TERT启动子突变相关的膀胱癌的病例对照研究,检索截至2024年11...目的:采用Meta分析评价TERT启动子突变和膀胱癌临床病理特征的关系。方法:检索Cochrane Library、Embase、PubMed、Web of Science、万方全文数据库、中国知网数据库,搜索与TERT启动子突变相关的膀胱癌的病例对照研究,检索截至2024年11月。两名研究人员独立筛选文献、提取信息、整理数据、评估纳入研究的偏倚风险,然后使用Review Manager 5.3进行汇总分析。结果:经数据库检索后,共检索到1575篇文献,排除综述论文、会议论文和无关研究等文献后,最终共纳入8篇文献,共1130例患者。Meta分析结果表明,TERT启动子突变与性别之间存在关联,男性患者比女性患者更易发生TERT启动子突变。结论:与女性膀胱癌患者相比,男性膀胱癌患者更容易出现TERT启动突变,这暗示了膀胱癌中存在与性别相关的潜在分子机制,为实验室和临床肿瘤研究提供了新的方向。Objective: To evaluate the relationship between TERT promoter mutations and clinical pathological features of bladder cancer using a Meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases for case-control studies on TERT promoter mutations in bladder cancer, with data up to November 2024. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was conducted using Review Manager 5.3. Results: A total of 1575 studies were identified through database searches. After excluding review articles, conference papers, and irrelevant studies, 8 studies with a total of 1130 patients were included. The Meta-analysis results showed that TERT promoter mutations are somewhat related to gender, with males being more likely to have TERT promoter mutations than females. Conclusion: Male bladder cancer patients are more likely to experience TERT promoter mutations compared to female bladder cancer patients. This suggests the presence of gender-related potential molecular mechanisms in bladder cancer, providing new insights for laboratory and clinical cancer research.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,su...BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.展开更多
文摘目的:采用Meta分析评价TERT启动子突变和膀胱癌临床病理特征的关系。方法:检索Cochrane Library、Embase、PubMed、Web of Science、万方全文数据库、中国知网数据库,搜索与TERT启动子突变相关的膀胱癌的病例对照研究,检索截至2024年11月。两名研究人员独立筛选文献、提取信息、整理数据、评估纳入研究的偏倚风险,然后使用Review Manager 5.3进行汇总分析。结果:经数据库检索后,共检索到1575篇文献,排除综述论文、会议论文和无关研究等文献后,最终共纳入8篇文献,共1130例患者。Meta分析结果表明,TERT启动子突变与性别之间存在关联,男性患者比女性患者更易发生TERT启动子突变。结论:与女性膀胱癌患者相比,男性膀胱癌患者更容易出现TERT启动突变,这暗示了膀胱癌中存在与性别相关的潜在分子机制,为实验室和临床肿瘤研究提供了新的方向。Objective: To evaluate the relationship between TERT promoter mutations and clinical pathological features of bladder cancer using a Meta-analysis. Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases for case-control studies on TERT promoter mutations in bladder cancer, with data up to November 2024. Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was conducted using Review Manager 5.3. Results: A total of 1575 studies were identified through database searches. After excluding review articles, conference papers, and irrelevant studies, 8 studies with a total of 1130 patients were included. The Meta-analysis results showed that TERT promoter mutations are somewhat related to gender, with males being more likely to have TERT promoter mutations than females. Conclusion: Male bladder cancer patients are more likely to experience TERT promoter mutations compared to female bladder cancer patients. This suggests the presence of gender-related potential molecular mechanisms in bladder cancer, providing new insights for laboratory and clinical cancer research.
基金Supported by National Natural Science Foundation of China,No.82000792General Project of Chongqing Natural Science Foundation,No.CSTB2023NSCQ-MSX0246 and No.CSTB2022NSCQ-MSX1271+1 种基金Research Project of the State Administration of Traditional Chinese Medicine on Collaborative Chronic Disease Management of Traditional Chinese Medicine and Western Medicine,No.CXZH2024087Science and Health Joint Project of Dazu District Science and Technology Bureau,No.DZKJ2024JSYJ-KWXM1002.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is a severe global health problem that causes prolonged disease exposure and an elevated risk for chronic complications,posing a substantial health burden.Although therapies,such as GLP-1 receptor agonists and SGLT2 inhibitors,have been successfully developed,new therapeutic options are still expected to offer better blood glucose control and decrease complications.AIM To elucidate the mechanism by which TERT/FOXO1 affects high glucose(HG)-induced dysfunction in isletβ-cells via the regulation of ATG9A-mediated autophagy.METHODS High-fat diet(HFD)-fed/streptozotocin(STZ)-treated mice or HG-treated MIN6 cells were used to establish T2DM models.Fasting blood glucose(FBG)and insulin levels in mice,as well as morphological changes in islet tissues,were assessed.Cell proliferation and the apoptosis rate were measured via EdU assays and flow cytometry,respectively.The expression levels of TERT,FOXO1,ATG9A and autophagy-related proteins(LC3B,p62)were analyzed via western blotting.The relationship between FOXO1 and ATG9A was assessed using dual-luciferase reporter gene assays and ChIP assays.RESULTS T2DM modeling in HFD-fed/STZ-treated mice and HG-treated MIN6 cells led to elevated TERT and FOXO1 expression and reduced ATG9A expression.Mice with T2DM were found to have decreased body weight,worsened morphology,elevated FBG and suppressed insulin levels.HG-treated MIN6 cells presented decreased viability and LC3B expression,in addition to increased p62 expression and apoptosis rates.FOXO1 knockdown both in vitro and in vivo protected mice and cells against isletβ-cell dysfunction via the activation of autophagy.The molecular mechanism involved the suppression of ATG9A expression by TERT through FOXO1 transcription activation.CONCLUSION Our results suggested that TERT/FOXO1 inhibits ATG9A expression to decrease isletβ-cell function in T2DM.
