miR-1271 Regulates Cisplatin Resistance of Human Gastric Cancer Cell Lines by Targeting IGF1R, IRS1, mTOR, and BCL2
miR-1271 Regulates Cisplatin Resistance of Human Gastric Cancer Cell Lines by Targeting IGF1R, IRS1, mTOR, and BCL2
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miR-1271 通过靶向 IGF1R、IRS1、mTOR 和 BCL2 调节人胃癌细胞系的顺铂耐药性
DOI：
10.2174/1871520614666140528161318
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发表时间：
2014-01-01
影响因子：
2.8
通讯作者：
Liu, Ping
中科院分区：
文献类型：
--
作者：
Yang, Mifang;Shan, Xia;Liu, Ping
大量研究表明，胃癌细胞的耐药性可通过靶向多个细胞信号通路的microRNAs（miRNAs）的异常表达来调控。本研究探讨了miR-1271在胃癌细胞顺铂耐药形成中的可能作用。miR-1271在胃癌组织和多种胃癌细胞系中表达显著下调。此外，它在顺铂耐药胃癌细胞系SGC 7901/顺铂（DDP）中下调，并且在SGC 7901/DPP细胞中miR-1271的下调伴随着胰岛素样生长因子1受体（IGF 1 R）/胰岛素受体底物1（IRS 1）通路相关蛋白的上调，即，IGF 1 R、IRS 1、丝氨酸/苏氨酸蛋白激酶mTOR（mTOR）和凋亡调节因子Bcl-2（BCL 2）。过表达miR-1271可使胃癌细胞对顺铂敏感。在SGC 7901/DDP细胞中，携带上述蛋白的3'非翻译区的报告构建体的荧光素酶活性的变化表明IGF 1 R、IRS 1、mTOR和BCL 2是miR-1271的靶基因。miR-1271的高表达抑制了靶蛋白的表达，抑制了胃癌细胞的增殖，并使胃癌细胞对DDP诱导的凋亡敏感。综上所述，我们认为miR-1271至少部分地通过靶向IGF 1 R/IRS 1通路调节人胃癌细胞顺铂耐药。
Numerous studies showed that drug resistance of gastric cancer cells could be modulated by the abnormal expression of microRNAs (miRNAs) which target multiple cell signaling pathways. The possible function of miR-1271 in the formation of cisplatin resistance in gastric cancer cells has been investigated in this study. miR-1271 was significantly down-regulated in gastric cancer tissues and various gastric cancer cell lines. Moreover, it was down-regulated in the cisplatin-resistant gastric cancer cell line SGC7901/cisplatin (DDP) and the down-regulation of miR-1271 in SGC7901/DPP cells was accompanied by the up-regulation of insulin-like growth factor 1 receptor (IGF1R)/insulin receptor substrate 1 (IRS1) pathway-related proteins, i.e., IGF1R, IRS1, serine/threonine-protein kinase mTOR (mTOR), and the apoptosis regulator Bcl-2 (BCL2), compared with the parental SGC7901 cells. Over-expression of miR-1271 sensitized SGC7901/DDP cells to cisplatin. Changes in the luciferase activity of reporter constructs harboring the 3' -untranslated region of the above proteins in SGC7901/DDP cells suggested that IGF1R, IRS1, mTOR, and BCL2 were target genes of miR-1271. Enforced miR-1271 expression repressed the protein levels of its targets, inhibited proliferation of SGC7901/DDP cells, and sensitized SGC7901/DDP cells to DDP-induced apoptosis. Overall, on the basis of the results of our study, we proposed that miR-1271 could regulate cisplatin resistance in human gastric cancer cells, at least partially, via targeting the IGF1R/IRS1 pathway.