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

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....

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Autores principales: Zhao, Ci, Zhao, Qi, Zhang, Chunhui, Wang, Guangyu, Yao, Yuanfei, Huang, Xiaoyi, Zhan, Fei, Zhu, Yuanyuan, Shi, Jiaqi, Chen, Jianan, Yan, Feihu, Zhang, Yanqiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482850/
https://www.ncbi.nlm.nih.gov/pubmed/28646148
http://dx.doi.org/10.1038/s41598-017-04172-z
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author Zhao, Ci
Zhao, Qi
Zhang, Chunhui
Wang, Guangyu
Yao, Yuanfei
Huang, Xiaoyi
Zhan, Fei
Zhu, Yuanyuan
Shi, Jiaqi
Chen, Jianan
Yan, Feihu
Zhang, Yanqiao
author_facet Zhao, Ci
Zhao, Qi
Zhang, Chunhui
Wang, Guangyu
Yao, Yuanfei
Huang, Xiaoyi
Zhan, Fei
Zhu, Yuanyuan
Shi, Jiaqi
Chen, Jianan
Yan, Feihu
Zhang, Yanqiao
author_sort Zhao, Ci
collection PubMed
description 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.
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spelling pubmed-54828502017-06-26 miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis Zhao, Ci Zhao, Qi Zhang, Chunhui Wang, Guangyu Yao, Yuanfei Huang, Xiaoyi Zhan, Fei Zhu, Yuanyuan Shi, Jiaqi Chen, Jianan Yan, Feihu Zhang, Yanqiao Sci Rep Article 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. Nature Publishing Group UK 2017-06-23 /pmc/articles/PMC5482850/ /pubmed/28646148 http://dx.doi.org/10.1038/s41598-017-04172-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhao, Ci
Zhao, Qi
Zhang, Chunhui
Wang, Guangyu
Yao, Yuanfei
Huang, Xiaoyi
Zhan, Fei
Zhu, Yuanyuan
Shi, Jiaqi
Chen, Jianan
Yan, Feihu
Zhang, Yanqiao
miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482850/
https://www.ncbi.nlm.nih.gov/pubmed/28646148
http://dx.doi.org/10.1038/s41598-017-04172-z
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