miR-195 enhances the radiosensitivity of colorectal cancer cells by suppressing CARM1
Authors Zheng L, Chen J, Zhou Z, He Z
Received 18 October 2016
Accepted for publication 5 January 2017
Published 20 February 2017 Volume 2017:10 Pages 1027—1038
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Lucy Goodman
Peer reviewer comments 4
Editor who approved publication: Dr Jianmin Xu
Li Zheng,* Jiangtao Chen,* Zhongyong Zhou, Zhikuan He
Department of General Surgery, Huaihe Hospital of Henan University, Kaifeng, People’s Republic of China
*These authors contributed equally to this work
Background: microRNAs (miRNAs) can regulate the sensitivity of cancer cells to chemotherapy and radiotherapy. Aberrant expression of miR-195 has been found to be involved in colorectal cancer (CRC); however, its function and underlying mechanism in the radioresistance of CRC remains unclear.
Methods: The levels of miR-195 and CARM1 were detected by quantitative reverse transcription-polymerase chain reaction and Western blot analysis in HCT-116 and HT-29 cells, respectively. Colony survival and apoptosis were determined by clonogenic assay and flow cytometry analysis, respectively. The apoptosis-related proteins Bax, Bcl-2, and γ-H2AX were detected using Western blot. The targets of miR-195 were identified by bioinformatic prediction and luciferase reporter assays. CRC cells in vitro and in vivo were exposed to different doses of X-ray radiations.
Results: miR-195 was downregulated, and CARM1 was upregulated in HCT-116 and HT-29 cells. miR-195 overexpression or CARM1 knockdown suppressed colony survival, induced apoptosis, promoted expression of Bax and γ-H2AX, and inhibited Bcl-2 expression in CRC cells. CARM1 was identified and validated to be a functional target of miR-195. Moreover, restored expression of CARM1 reversed the enhanced radiosensitivity of CRC cells induced by miR-195. Furthermore, miR-195 increased the sensitivity of CRC cells to radiation in vivo.
Conclusion: miR-195 enhances radiosensitivity of CRC cells through suppressing CARM1. Therefore, miR-195 acts as a potential regulator of radioresistance for CRC cells and as a promising therapeutic target for CRC patients.
Keywords: miR-195, CARM1, colorectal cancer, radiosensitivity
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