1. miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
- Author
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Xie, Xu-Qin, Wang, Mo-Jin, Li, Yuan, Lei, Lin-Ping, Wang, Ning, Lv, Zhao-Ying, Chen, Ke-Ling, Zhou, Bin, Ping, Jie, Zhou, Zong-Guang, Sun, Xiao-Feng, Xie, Xu-Qin, Wang, Mo-Jin, Li, Yuan, Lei, Lin-Ping, Wang, Ning, Lv, Zhao-Ying, Chen, Ke-Ling, Zhou, Bin, Ping, Jie, Zhou, Zong-Guang, and Sun, Xiao-Feng
- Abstract
Our previous study demonstrated that miR-124 was downregulated in colorectal cancer (CRC) compared with normal mucosa, and the downregulated expression of miR-124 was an independent prognostic factor in CRC patients. However, the function of miR-124 in CRC patients treated with chemotherapy is currently unclear. The aim of this study was to determine the miR-124 expression and its regulative role in oxaliplatin (L-OHP)-based chemotherapy of CRC patients. We observed that low miR-124 expression was correlated with worse overall survival (OS) in the 220 patients who received postoperative chemotherapy of 5-fluorouracil [5-FU] +leucovorin+L-OHP (FOLFOX) or capecitabine+L-OHP (XELOX). miR-124 overexpression promoted L-OHP-induced, but not 5-FU-induced, cytotoxicity and apoptosis in HT29 and SW480 cells. CAPN2 was a direct target of miR124, and its protein expression was reduced by forced expression of miR-124. miR-124 inhibited tumorigenesis and promoted OS of mice bearing xenograft tumors, especially upon L-OHP treatment. miR-124 also promoted L-OHP-induced apoptosis and restrained CAPN2 protein expression in xenograft tumors. Our results suggest that miR-124 could be considered as both a predictor of L-OHP-based chemotherapy for personalized treatment and a therapeutic target for CRC., Funding Agencies|National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81401949, 81300359]; Key Research Projects of the Department of Science and Technology of Sichuan Province, China [2018SZ0403]
- Published
- 2020
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