Background: Trastuzumab resistance accounts for chemotherapy failure in gastric cancer patients in clinicalpractice. The significance of long non-coding RNAs (lncRNAs) in the maintenance of drug resistance in gastricc...Background: Trastuzumab resistance accounts for chemotherapy failure in gastric cancer patients in clinicalpractice. The significance of long non-coding RNAs (lncRNAs) in the maintenance of drug resistance in gastriccancer has been already underlined. Method: This study aimed to identify the specific role of lncRNA-ATB in gastriccancer progression and trastuzumab resistance. The downstream miRs of lncRNA-ATB and target genes of miRs werepredicted by bioinformatics analysis and verified using dual luciferase reporter assay. Loss- and gain-function assayswere performed to explore the roles of lncRNA-ATB, miR-200c, and zinc-finger protein 217 (ZNF217) in the cellfunctions and trastuzumab resistance of a trastuzumab-resistant gastric cancer cell line (NCI-N87-TR). Result:LncRNA-ATB was upregulated, while miR-200c was downregulated. Depletion of lncRNA-ATB or miR-200celevation led to a decrease in malignant properties of NCI-N87-TR cells. LncRNA-ATB could negatively target miR-200c, which in turn inversely targeted and reduced the expression of ZNF217. Silencing of ZNF217 could inhibit cellviability and migration. Conclusion: lncRNA-ATB promoted the progression and trastuzumab resistance of gastriccancer by repressing miR-200c via ZNF217 upregulation.展开更多
目的:探讨miR-200c在胃癌组织中的表达水平与胃癌患者临床病理特征及无病生存期(diease free survial,DFS)的关系。方法:收集河北医科大学第四医院普外科2012年5月至2013年1月64例胃癌手术切除的标本及相关临床资料,采用实时荧光定量PC...目的:探讨miR-200c在胃癌组织中的表达水平与胃癌患者临床病理特征及无病生存期(diease free survial,DFS)的关系。方法:收集河北医科大学第四医院普外科2012年5月至2013年1月64例胃癌手术切除的标本及相关临床资料,采用实时荧光定量PCR技术检测miR-200c在胃癌组织和配对癌旁非癌组织中的表达。回顾性分析miR-200c表达水平与胃癌患者的临床病理特征及DFS相关性。结果:胃癌组织中miR-200c的表达水平显著低于癌旁非癌组织(3.29 vs 5.91,P<0.01)。miR-200c的表达水平与肿瘤TNM分期、浸润深度、转移和脉管瘤栓呈显著负相关(均P<0.01)。miR-200c高表达组患者中位DFS明显长于低表达组患者(22.0 vs 13.5个月,P<0.01),其表达水平与患者DFS呈正相关(P<0.01)。结论:miR-200c在胃癌组织中低表达,其表达水平与肿瘤TNM分期、肿瘤浸润深度和脉管瘤栓呈负相关,与DFS呈正相关,在胃癌的发生发展及预后中具有重要作用。展开更多
基金supported by grants from the Basic Scientific Research Fund for Heilongjiang Provincial Universities in 2018(2018-KYYWF-0105).
文摘Background: Trastuzumab resistance accounts for chemotherapy failure in gastric cancer patients in clinicalpractice. The significance of long non-coding RNAs (lncRNAs) in the maintenance of drug resistance in gastriccancer has been already underlined. Method: This study aimed to identify the specific role of lncRNA-ATB in gastriccancer progression and trastuzumab resistance. The downstream miRs of lncRNA-ATB and target genes of miRs werepredicted by bioinformatics analysis and verified using dual luciferase reporter assay. Loss- and gain-function assayswere performed to explore the roles of lncRNA-ATB, miR-200c, and zinc-finger protein 217 (ZNF217) in the cellfunctions and trastuzumab resistance of a trastuzumab-resistant gastric cancer cell line (NCI-N87-TR). Result:LncRNA-ATB was upregulated, while miR-200c was downregulated. Depletion of lncRNA-ATB or miR-200celevation led to a decrease in malignant properties of NCI-N87-TR cells. LncRNA-ATB could negatively target miR-200c, which in turn inversely targeted and reduced the expression of ZNF217. Silencing of ZNF217 could inhibit cellviability and migration. Conclusion: lncRNA-ATB promoted the progression and trastuzumab resistance of gastriccancer by repressing miR-200c via ZNF217 upregulation.
文摘目的:探讨miR-200c在胃癌组织中的表达水平与胃癌患者临床病理特征及无病生存期(diease free survial,DFS)的关系。方法:收集河北医科大学第四医院普外科2012年5月至2013年1月64例胃癌手术切除的标本及相关临床资料,采用实时荧光定量PCR技术检测miR-200c在胃癌组织和配对癌旁非癌组织中的表达。回顾性分析miR-200c表达水平与胃癌患者的临床病理特征及DFS相关性。结果:胃癌组织中miR-200c的表达水平显著低于癌旁非癌组织(3.29 vs 5.91,P<0.01)。miR-200c的表达水平与肿瘤TNM分期、浸润深度、转移和脉管瘤栓呈显著负相关(均P<0.01)。miR-200c高表达组患者中位DFS明显长于低表达组患者(22.0 vs 13.5个月,P<0.01),其表达水平与患者DFS呈正相关(P<0.01)。结论:miR-200c在胃癌组织中低表达,其表达水平与肿瘤TNM分期、肿瘤浸润深度和脉管瘤栓呈负相关,与DFS呈正相关,在胃癌的发生发展及预后中具有重要作用。