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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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) |
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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 |
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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 |
work_keys_str_mv |
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