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

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.

Keywords: drug resistance; gastric cancer; microRNA-17-5p; p21.