Research Paper|Volume 8, Issue 7|pp 1442—1456

miR-638 suppresses DNA damage repair by targeting SMC1A expression in terminally differentiated cells

Mingyang He¹, Yi Lin¹, Yunlan Tang¹, Yi Liu¹, Weiwei Zhou¹, Chuang Li¹, Guihong Sun², Mingxiong Guo¹

¹College of Life Sciences, Wuhan University, 430072 Wuhan, P. R. China
²School of Basic Medical Sciences, Wuhan University, 430071 Wuhan, P.R. China

Received: April 25, 2016Accepted: June 28, 2016Published: July 12, 2016

Copyright: © 2016 He et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The reduction of DNA damage repair capacity in terminally differentiated cells may be involved in sensitivity to cancer chemotherapy drugs; however, the underlying molecular mechanism is still not fully understood. Herein, we evaluated the role of miR-638 in the regulation of DNA damage repair in terminally differentiated cells. Our results show that miR-638 expression was up-regulated during cellular terminal differentiation and involved in mediating DNA damage repair processes. Results from a luciferase reporting experiment show that structural maintenance of chromosomes (SMC)1A was a potential target of miR-638; this was verified by western blot assays during cell differentiation and DNA damage induction. Overexpression of miR-638 enhanced the sensitivity of cancer cells to cisplatin, thus reducing cell viability in response to chemotherapy drug treatment. Furthermore, miR-638 overexpression affected DNA damage repair processes by interfering with the recruitment of the DNA damage repair-related protein, γH2AX, to DNA break sites. These findings indicate that miR-638 might act as a sensitizer in cancer chemotherapy and accompany chemotherapy drugs to enhance chemotherapeutic efficacy and to improve the chance of recovery from cancer.