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miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer.

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机构： [1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China [2]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China [3]The First Affiliated Hospital of Dali University, 32 Jiashibo Avenue, Dali 671000, Yunnan Province, China [4]Division of Epidemiology, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 800, Nashville, TN 37203-1738, USA [5]Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden

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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 miR-124, 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. © 2020 The Author(s).

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出版当年[2020]版：

大类 | 2 区医学

小类 | 2 区肿瘤学 2 区医学：研究与实验

最新[2023]版：

大类 | 2 区医学

小类 | 2 区医学：研究与实验 3 区肿瘤学

第一作者：

第一作者机构： [1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China

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通讯作者：

通讯机构： [1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China [2]Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China [5]Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden [*1]Institute of Digestive Surgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China. [*2]Department of Oncology and Department of Biomedical and Clinical Sciences, Linköping University, 581 83 Linköping, Sweden.

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