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 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.
Highlights
Colorectal cancer (CRC) has been a serious public health problem worldwide for many years because of its frequency, despite the screening and preventive strategies
To the best of our knowledge, this is the first study to demonstrate the relationship between miR-124 expression and the chemotherapy of colorectal cancer (CRC) patients
We found that low miR-124 expression was significantly correlated with worse overall survival (OS) in CRC patients who received FOLFOX or XELOX
Summary
Colorectal cancer (CRC) has been a serious public health problem worldwide for many years because of its frequency, despite the screening and preventive strategies. MicroRNAs (miRNAs) belong to a group of small non-coding RNAs of 18–24 nt that are known to significantly regulate gene expression, posttranslational repression, or cleavage of mRNA targets.[3] Most miRNAs behave as oncogenes or tumor suppressor genes, depending on the target mRNA, and they play a role in the pathogenicity of various malignancies.[4] More and more molecular studies indicate a closer link between miRNA functions and CRC pathogenesis, including oncogene activation and anti-oncogene inactivation, influencing proliferation and apoptosis, and regulation of pathogenesis. Investigation of these miRNAs would expand our view to better understand CRC carcinogenesis
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