miRNAs are endogenous small RNAs that are important regulators of gene expression.miR-1294 was found to be significantly down-regulated in 15 cancers and regulated by 21 upstream regulators.miR-1294 affects the prolif...miRNAs are endogenous small RNAs that are important regulators of gene expression.miR-1294 was found to be significantly down-regulated in 15 cancers and regulated by 21 upstream regulators.miR-1294 affects the proliferation,migration,invasion,and apoptosis of cancer cells.The target genes of miR-1294 are involved in the PI3K/AKT/mTOR,RAS,and JAK/STAT signaling pathways.Six target genes of miR-1294 are the targets of a variety of drugs.Low expression of miR-1294 is associated with resistance to cisplatin and TMZ and a poorer prognosis in patients with ESCC,GC,EOC,PDAC,or NSCLC.Therefore,this work outlines the molecular mechanisms and provides a basis for the clinical significance of the tumor suppressor miR-1294 in cancer.展开更多
目的:探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)患者血清miR-1294及miR-4443的表达水平及其与患者临床病理特征和预后的关系。方法:选取我院2015年1月至2017年12月收治的106例EOC患者作为EOC组,另选取90例卵巢良性肿瘤患者作为...目的:探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)患者血清miR-1294及miR-4443的表达水平及其与患者临床病理特征和预后的关系。方法:选取我院2015年1月至2017年12月收治的106例EOC患者作为EOC组,另选取90例卵巢良性肿瘤患者作为良性组和60例正常健康女性作为对照组,检测血清miR-1294及miR-4443表达水平。以miR-1294及miR-4443的最佳截断值为标准将EOC患者分为高miR-1294组(n=33)、低miR-1294组(n=73)和高miR-4443组(n=36)、低miR-4443组(n=70)。EOC患者预后不良的危险因素应用单因素及多因素COX回归模型进行分析。结果:血清miR-1294表达水平(0.48±0.13 vs 1.16±0.57、1.21±0.62)在EOC组明显低于良性组和对照组(P均<0.001)。血清miR-4443表达水平(0.71±0.18 vs 1.36±0.64、1.45±0.70)在EOC组明显低于良性组和对照组(P均<0.001)。miR-1294和miR-4443高表达组的EOC患者临床分期、分化程度、淋巴结转移及腹膜转移与miR-1294和miR-4443低表达组比较,差异均有统计学意义(P<0.05)。Kaplan-Meier分析显示,EOC患者生存期短与miR-1294及miR-4443低表达有关(P<0.001)。多因素分析显示,EOC患者预后不良的独立危险因素为淋巴结转移[HR(95%CI)=1.885(1.206~4.118)]、腹膜转移[HR(95%CI)=3.106(2.315~6.226)]、miR-1294<0.73[HR(95%CI)=2.614(1.865~5.512)]及miR-4443<1.04[HR(95%CI)=1.975(1.508~4.903)]。结论:miR-1294及miR-4443的低表达与EOC患者生存期短有关,是EOC患者预后预测的生物标志物。展开更多
Non-smallcell lung cancer(NSCLC)cells intake and consume glucose at high efficiency by aerobic glycolysis to maintain robust cell growth and resist cell death.MicroRNAs(miRNAs)have been known to play pivotal roles in ...Non-smallcell lung cancer(NSCLC)cells intake and consume glucose at high efficiency by aerobic glycolysis to maintain robust cell growth and resist cell death.MicroRNAs(miRNAs)have been known to play pivotal roles in NSCLC development partly through mediating glycolysis.However,only a few miRNAs have been experimentally confirmed as critical regulators of glycolysis in NSCLC.TCGA datasets were analyzed to screen for differentially expressed miRNAs between NSCLC and normal tissues.The function of miR-1294-5p was determined in NSCLC cells by cell proliferation,glucose uptake,lactate release,and Extracellular Acidification Rate(ECAR)assays.The target of miR-1294-5p was predicted by TargetScan and miRDB,which was further validated by flow cytometry analysis,RT-qPCR,western blotting,a dual-luciferase reporter assay,and RNA immunoprecipitation(RIP)assay.In the present study,it was found that miR-1294-5p was a significantly downregulated miRNA in lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC).The overexpression of miR-1294-5p inhibited glycolysis,lactate export,ECAR,and cell proliferation in NSCLC cells.Analysis with bioinformatic tools,Western Blotting,RT-qPCR,flow cytometry analysis,dual-luciferase reporter assay,and RIP assay showed that miR-1294-5p directly bound to complementary sites in the 3’-Untranslated Region(UTR)of TMPRSS11B resulted in downregulation of TMPRSS11B expression.In addition,transfection of recombinant TMPRSS11B rescued the functions of miR-1294-5p on glycolysis and proliferation of NSCLC cells.The findings provided novel insights for understanding the regulation of glycolytic metabolism in NSCLC.展开更多
基金supported by Qiantang Scholarship in Zhejiang University City College,Hangzhou Agricultural and Social Development Research Project(2020ZDSJ0637).
文摘miRNAs are endogenous small RNAs that are important regulators of gene expression.miR-1294 was found to be significantly down-regulated in 15 cancers and regulated by 21 upstream regulators.miR-1294 affects the proliferation,migration,invasion,and apoptosis of cancer cells.The target genes of miR-1294 are involved in the PI3K/AKT/mTOR,RAS,and JAK/STAT signaling pathways.Six target genes of miR-1294 are the targets of a variety of drugs.Low expression of miR-1294 is associated with resistance to cisplatin and TMZ and a poorer prognosis in patients with ESCC,GC,EOC,PDAC,or NSCLC.Therefore,this work outlines the molecular mechanisms and provides a basis for the clinical significance of the tumor suppressor miR-1294 in cancer.
文摘目的:探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)患者血清miR-1294及miR-4443的表达水平及其与患者临床病理特征和预后的关系。方法:选取我院2015年1月至2017年12月收治的106例EOC患者作为EOC组,另选取90例卵巢良性肿瘤患者作为良性组和60例正常健康女性作为对照组,检测血清miR-1294及miR-4443表达水平。以miR-1294及miR-4443的最佳截断值为标准将EOC患者分为高miR-1294组(n=33)、低miR-1294组(n=73)和高miR-4443组(n=36)、低miR-4443组(n=70)。EOC患者预后不良的危险因素应用单因素及多因素COX回归模型进行分析。结果:血清miR-1294表达水平(0.48±0.13 vs 1.16±0.57、1.21±0.62)在EOC组明显低于良性组和对照组(P均<0.001)。血清miR-4443表达水平(0.71±0.18 vs 1.36±0.64、1.45±0.70)在EOC组明显低于良性组和对照组(P均<0.001)。miR-1294和miR-4443高表达组的EOC患者临床分期、分化程度、淋巴结转移及腹膜转移与miR-1294和miR-4443低表达组比较,差异均有统计学意义(P<0.05)。Kaplan-Meier分析显示,EOC患者生存期短与miR-1294及miR-4443低表达有关(P<0.001)。多因素分析显示,EOC患者预后不良的独立危险因素为淋巴结转移[HR(95%CI)=1.885(1.206~4.118)]、腹膜转移[HR(95%CI)=3.106(2.315~6.226)]、miR-1294<0.73[HR(95%CI)=2.614(1.865~5.512)]及miR-4443<1.04[HR(95%CI)=1.975(1.508~4.903)]。结论:miR-1294及miR-4443的低表达与EOC患者生存期短有关,是EOC患者预后预测的生物标志物。
文摘Non-smallcell lung cancer(NSCLC)cells intake and consume glucose at high efficiency by aerobic glycolysis to maintain robust cell growth and resist cell death.MicroRNAs(miRNAs)have been known to play pivotal roles in NSCLC development partly through mediating glycolysis.However,only a few miRNAs have been experimentally confirmed as critical regulators of glycolysis in NSCLC.TCGA datasets were analyzed to screen for differentially expressed miRNAs between NSCLC and normal tissues.The function of miR-1294-5p was determined in NSCLC cells by cell proliferation,glucose uptake,lactate release,and Extracellular Acidification Rate(ECAR)assays.The target of miR-1294-5p was predicted by TargetScan and miRDB,which was further validated by flow cytometry analysis,RT-qPCR,western blotting,a dual-luciferase reporter assay,and RNA immunoprecipitation(RIP)assay.In the present study,it was found that miR-1294-5p was a significantly downregulated miRNA in lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC).The overexpression of miR-1294-5p inhibited glycolysis,lactate export,ECAR,and cell proliferation in NSCLC cells.Analysis with bioinformatic tools,Western Blotting,RT-qPCR,flow cytometry analysis,dual-luciferase reporter assay,and RIP assay showed that miR-1294-5p directly bound to complementary sites in the 3’-Untranslated Region(UTR)of TMPRSS11B resulted in downregulation of TMPRSS11B expression.In addition,transfection of recombinant TMPRSS11B rescued the functions of miR-1294-5p on glycolysis and proliferation of NSCLC cells.The findings provided novel insights for understanding the regulation of glycolytic metabolism in NSCLC.
