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微小RNA-17-5p的下调通过靶向p21部分抑制胃癌细胞的耐药性。

Downregulation of microRNA-17-5p inhibits drug resistance of gastric cancer cells partially through targeting p21.

作者信息

Wang Ziwei, Ji Feng

机构信息

Department of Internal Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.

Department of Digestive Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):4585-4591. doi: 10.3892/ol.2018.7822. Epub 2018 Jan 19.

Abstract

MicroRNAs (miRNAs/miRs) are endogenous small non-coding RNAs that post-transcriptionally regulate the expression of genes and serve crucial roles in diverse biological processes. The present study aimed to examine the miRNA expression profile and drug resistance in the SGC7901 cell line and its isogenic drug-resistant counterpart, SGC7901/cisplatin (DDP) cell line. The potential role of miR-17-5p in modulating drug resistance in gastric cancer cells was investigated. Different levels of miRNA expression between SGC7901/DDP and SGC7901 cells were analyzed by miRNA microarray and validated by quantitative polymerase chain reaction. It was indicated that the downregulation of miR-17-5p sensitized SGC7901/DDP cells to anticancer drugs. A decreased luciferase activity of p21 3'-untranslated region-based reporter in miR-17-5p-transfected SGC7901/DDP cells suggested that p21 may be a direct target gene of miR-17-5p. Western blot analysis and flow cytometric assay revealed that the downregulation of miR-17-5p increases the sensitivity of SGC7901/DDP cells to DDP-induced apoptosis. Taken together, these results demonstrated that miR-17-5p may perform a role in the development of drug resistance in gastric cancer cells, at least partially by modulating apoptosis via targeting p21.

摘要

微小RNA(miRNA/miR)是内源性小非编码RNA,可在转录后调节基因表达,并在多种生物学过程中发挥关键作用。本研究旨在检测SGC7901细胞系及其同源耐药细胞系SGC7901/顺铂(DDP)细胞系中的miRNA表达谱和耐药性。研究了miR-17-5p在调节胃癌细胞耐药性中的潜在作用。通过miRNA微阵列分析SGC7901/DDP和SGC7901细胞之间不同水平的miRNA表达,并通过定量聚合酶链反应进行验证。结果表明,miR-17-5p的下调使SGC7901/DDP细胞对抗癌药物敏感。在转染miR-17-5p的SGC7901/DDP细胞中,基于p21 3'-非翻译区的报告基因的荧光素酶活性降低,提示p21可能是miR-17-5p的直接靶基因。蛋白质印迹分析和流式细胞术检测显示,miR-17-5p的下调增加了SGC7901/DDP细胞对DDP诱导凋亡的敏感性。综上所述,这些结果表明miR-17-5p可能在胃癌细胞耐药性的发展中发挥作用,至少部分是通过靶向p21调节细胞凋亡来实现的。

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