miR-138-5p modulates the expression of excision repair cross-complementing proteins ERCC1 and ERCC4, and regulates the sensitivity of gastric cancer cells to cisplatin
miR-138-5p modulates the expression of excision repair cross-complementing proteins ERCC1 and ERCC4, and regulates the sensitivity of gastric cancer cells to cisplatin
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DOI：
10.3892/or.2018.6907
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发表时间：
2019-02-01
期刊：
影响因子：
4.2
通讯作者：
Gu, Kangsheng
中科院分区：
文献类型：
--
作者：
Ning, Jie;Jiao, Yang;Gu, Kangsheng
microRNA（miR）-138-5p影响几种人类癌症类型的化疗敏感性。本研究旨在探讨miR-138- 5 p在胃癌细胞系SGC 7901及其顺铂耐药衍生物SGC 7901/DDP中的表达及其调控机制。基因芯片和逆转录-定量聚合酶链反应（RT-PCR）分析显示，miR-138- 5 p在胃癌细胞系SGC 7901/DDP中的表达水平明显低于胃癌细胞系SGC 7901。使用计算预测算法，鉴定了参与核切除修复途径的两种蛋白质，切除修复交叉互补（ERCC）1和ERCC 4，作为推定的miR-138- 5 p靶基因。Western blot分析证实，胃癌细胞株SGC 7901和SGC 7901/DDP中ERCC 1和ERCC 4的表达水平与miR-138- 5 p的表达水平成反比。此外，ERCC 1和ERCC 4在表达miR-138- 5 p靶向短发夹RNA的SGC 7901细胞中上调，相反，在过表达miR-138- 5 p的SGC 7901/DDP细胞中下调，证实该miRNA调节ERCC蛋白水平。miR-138- 5 p沉默可增强SGC 7901细胞的顺铂耐药性，而miR-138- 5 p过表达可部分逆转SGC 7901/DDP细胞的顺铂耐药性。综上所述，这些数据表明miR-138- 5 p可能通过调节DNA修复蛋白ERCC 1和ERCC 4的表达来调节胃癌细胞对顺铂的敏感性。
The microRNA (miR)-138-5p affects the chemotherapeutic sensitivity of several human cancer types. In the present study, the expression and regulatory mechanisms of miR-138-5p were investigated in the gastric cancer cell line SGC7901 and its cisplatin-resistant derivative SGC7901/DDP. Gene microarray and reverse transcription-quantitative polymerase chain reaction analyses revealed that miR-138-5p was expressed at significantly lower levels in SGC7901/DDP compared with SGC7901 cells. Using computational predictive algorithms, two proteins involved in the nuclear excision repair pathway were identified, excision repair cross-complementing (ERCC)1 and ERCC4, as putative miR-138-5p target genes. Western blot analysis confirmed that ERCC1 and ERCC4 expression levels were inversely proportional to miR-138-5p levels in SGC7901 and SGC7901/DDP cells. Furthermore, ERCC1 and ERCC4 were upregulated in SGC7901 cells expressing miR-138-5p-targeting short hairpin RNA and, conversely, downregulated in SGC7901/DDP cells overexpressing miR-138-5p, confirming that this miRNA regulates ERCC protein levels. Notably, miR-138-5p silencing enhanced the cisplatin resistance of SGC7901 cells, while miR-138-5p overexpression partially reversed the cisplatin resistance of SGC7901/DDP cells. Taken together, these data suggest that miR-138-5p regulates the sensitivity of gastric cancer cells to cisplatin, possibly by modulating expression of the DNA repair proteins ERCC1 and ERCC4.