MicroRNA-191 modulates cisplatin-induced DNA damage response by targeting RCC2.

Cisplatin is a first-line chemotherapeutic agent for the treatment of many types of cancer, but the emergence of chemoresistance hinders its application. Thus, a better understanding of cisplatin-induced DNA damage response (DDR) would help to overcome this problem. Previously, we have identified a panel of microRNAs with altered expression after cisplatin treatment in HeLa cells. In the current study, we focused on one of them, miR-191, and investigated its function in cisplatin-induced DDR. We found that overexpression of miR-191 sensitized HeLa cells to the cytotoxic effects of cisplatin, resulted in decreased viable cells. However, overexpression of miR-191 did not cause changes in apoptotic cell ratio but rather induced significant G2/M arrest in HeLa cell treated with cisplatin. Additionally, enhanced cisplatin-induced DNA damage was observed. Through bioinformatic analysis and verified by dual-luciferase assay, it was demonstrated that the chromosome condensation 2 regulator (RCC2) gene is a target for miR-191 regulation. Furthermore, the downregulation of RCC2 by siRNA mimics the effects of miR-191, in which greater DNA damage was observed upon cisplatin treatment. Taken together, our study indicates that miR-191 may be an important player in cisplatin-induced DDR, and it elicits its function, at least partially, through the regulation of RCC2. © 2020 Federation of American Societies for Experimental Biology.

Citation

Xianrong Xu, Xiaofeng Zhou, Jianyun Zhang, Hongjuan Li, Yifei Cao, Xiaohua Tan, Xinqiang Zhu, Jun Yang. MicroRNA-191 modulates cisplatin-induced DNA damage response by targeting RCC2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2020 Oct;34(10):13573-13585

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PMID: 32803782

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