1. miR-21-mediated Radioresistance Occurs via Promoting Repair of DNA Double Strand Breaks
- Author
-
Xiangming Zhang, Ping Wang, Baocheng Hu, Shuofeng Hu, Jian Wang, Xiaomin Ying, Xiang Wang, Hongyan Wang, and Ya Wang
- Subjects
0301 basic medicine ,CDC25A ,DNA End-Joining Repair ,DNA Repair ,DNA repair ,Biology ,Radiation Tolerance ,Biochemistry ,Cell Line ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Cyclin D1 ,Neoplasms ,Radioresistance ,Animals ,Humans ,DNA Breaks, Double-Stranded ,Withdrawals/Retractions ,Molecular Biology ,Glycogen Synthase Kinase 3 beta ,Oncogene ,Recombinational DNA Repair ,Cell Biology ,Mice, Inbred C57BL ,Non-homologous end joining ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,chemistry ,Cancer research ,Homologous recombination ,DNA - Abstract
miR-21, as an oncogene that overexpresses in most human tumors, is involved in radioresistance; however, the mechanism remains unclear. Here, we demonstrate that miR-21-mediated radioresistance occurs through promoting repair of DNA double strand breaks, which includes facilitating both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR). The miR-21-promoted NHEJ occurs through targeting GSK3B (a novel target of miR-21), which affects the CRY2/PP5 pathway and in turn increases DNA-PKcs activity. The miR-21-promoted HRR occurs through targeting both GSK3B and CDC25A (a known target of miR-21), which neutralizes the effects of targeting GSK3B-induced CDC25A increase because GSK3B promotes degradation of both CDC25A and cyclin D1, but CDC25A and cyclin D1 have an opposite effect on HRR. A negative correlation of expression levels between miR-21 and GSK3β exists in a subset of human tumors. Our results not only elucidate miR-21-mediated radioresistance, but also provide potential new targets for improving radiotherapy.
- Published
- 2017