miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis

Abstract Drug resistance, which is closely correlated with an imbalance in apoptosis, endows colorectal cancer (CRC) with enhanced progression capacity irrespective of the treatment with therapeutics. We report that miR-15b-5p is a tumor suppressor whose level is globally decreased in CRC cells and...

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Autores principales: Ci Zhao, Qi Zhao, Chunhui Zhang, Guangyu Wang, Yuanfei Yao, Xiaoyi Huang, Fei Zhan, Yuanyuan Zhu, Jiaqi Shi, Jianan Chen, Feihu Yan, Yanqiao Zhang
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/c26aeba7297c45e4a2d7ad6e2b180596
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spelling oai:doaj.org-article:c26aeba7297c45e4a2d7ad6e2b1805962021-12-02T11:41:12ZmiR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis10.1038/s41598-017-04172-z2045-2322https://doaj.org/article/c26aeba7297c45e4a2d7ad6e2b1805962017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04172-zhttps://doaj.org/toc/2045-2322Abstract Drug resistance, which is closely correlated with an imbalance in apoptosis, endows colorectal cancer (CRC) with enhanced progression capacity irrespective of the treatment with therapeutics. We report that miR-15b-5p is a tumor suppressor whose level is globally decreased in CRC cells and tissues. Over-expression of miR-15b-5p not only promoted 5-fluorouracil (5-FU)-induced cellular apoptosis but also reversed the chemoresistance of 5-FU in vitro and in vivo. As a key mediator of inflammation-induced cancer, miR-15b-5p enhances these therapeutic effects are mainly attributed to targeting of the NF-κB signaling pathway through negative regulation of NF-κB1 and one of its kinase complexes IKK-α. miR-15b-5p mediates NF-ĸB regulation by targeting the anti-apoptosis protein XIAP in vitro. Together, these results establish an axis of miR-15b-mediated apoptosis regulation, which reverses chemoresistance and suppresses CRC progression. These findings suggest that miR-15b-5p may be a potential agent for CRC treatment, particularly for 5-FU-resistant CRC.Ci ZhaoQi ZhaoChunhui ZhangGuangyu WangYuanfei YaoXiaoyi HuangFei ZhanYuanyuan ZhuJiaqi ShiJianan ChenFeihu YanYanqiao ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ci Zhao
Qi Zhao
Chunhui Zhang
Guangyu Wang
Yuanfei Yao
Xiaoyi Huang
Fei Zhan
Yuanyuan Zhu
Jiaqi Shi
Jianan Chen
Feihu Yan
Yanqiao Zhang
miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
description Abstract Drug resistance, which is closely correlated with an imbalance in apoptosis, endows colorectal cancer (CRC) with enhanced progression capacity irrespective of the treatment with therapeutics. We report that miR-15b-5p is a tumor suppressor whose level is globally decreased in CRC cells and tissues. Over-expression of miR-15b-5p not only promoted 5-fluorouracil (5-FU)-induced cellular apoptosis but also reversed the chemoresistance of 5-FU in vitro and in vivo. As a key mediator of inflammation-induced cancer, miR-15b-5p enhances these therapeutic effects are mainly attributed to targeting of the NF-κB signaling pathway through negative regulation of NF-κB1 and one of its kinase complexes IKK-α. miR-15b-5p mediates NF-ĸB regulation by targeting the anti-apoptosis protein XIAP in vitro. Together, these results establish an axis of miR-15b-mediated apoptosis regulation, which reverses chemoresistance and suppresses CRC progression. These findings suggest that miR-15b-5p may be a potential agent for CRC treatment, particularly for 5-FU-resistant CRC.
format article
author Ci Zhao
Qi Zhao
Chunhui Zhang
Guangyu Wang
Yuanfei Yao
Xiaoyi Huang
Fei Zhan
Yuanyuan Zhu
Jiaqi Shi
Jianan Chen
Feihu Yan
Yanqiao Zhang
author_facet Ci Zhao
Qi Zhao
Chunhui Zhang
Guangyu Wang
Yuanfei Yao
Xiaoyi Huang
Fei Zhan
Yuanyuan Zhu
Jiaqi Shi
Jianan Chen
Feihu Yan
Yanqiao Zhang
author_sort Ci Zhao
title miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
title_short miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
title_full miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
title_fullStr miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
title_full_unstemmed miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
title_sort mir-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the nf-κb/xiap axis
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/c26aeba7297c45e4a2d7ad6e2b180596
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