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

Ning,Jie; Jiao,Yang; Xie,Xiaoque; Deng,Xuefei; Zhang,Yiyin; Yang,Yuexin; Zhao,Chenchen; Wang,Hua; Gu,Kangsheng

doi:10.3892/or.2018.6907

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

Authors:
- Jie Ning
- Yang Jiao
- Xiaoque Xie
- Xuefei Deng
- Yiyin Zhang
- Yuexin Yang
- Chenchen Zhao
- Hua Wang
- Kangsheng Gu
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Affiliations: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230032, P.R. China, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China
Published online on: December 6, 2018 https://doi.org/10.3892/or.2018.6907
Pages: 1131-1139

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Abstract

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.

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