OncoTargets and Therapy (Feb 2017)
miR-195 enhances the radiosensitivity of colorectal cancer cells by suppressing CARM1
Abstract
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
