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

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 curre...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200624/
https://www.ncbi.nlm.nih.gov/pubmed/32382656
http://dx.doi.org/10.1016/j.omto.2020.04.003
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author 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
author_facet 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
author_sort Xie, Xu-Qin
collection PubMed
description 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.
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spelling pubmed-72006242020-05-07 miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer 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 Mol Ther Oncolytics Article 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. American Society of Gene & Cell Therapy 2020-04-14 /pmc/articles/PMC7200624/ /pubmed/32382656 http://dx.doi.org/10.1016/j.omto.2020.04.003 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
title miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
title_full miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
title_fullStr miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
title_full_unstemmed miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
title_short miR-124 Intensified Oxaliplatin-Based Chemotherapy by Targeting CAPN2 in Colorectal Cancer
title_sort mir-124 intensified oxaliplatin-based chemotherapy by targeting capn2 in colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200624/
https://www.ncbi.nlm.nih.gov/pubmed/32382656
http://dx.doi.org/10.1016/j.omto.2020.04.003
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