miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis.
miR-15b-5p resensitizes colon cancer cells to 5-fluorouracil by promoting apoptosis via the NF-κB/XIAP axis.
复制标题
miR-15b-5p 通过 NF-kappa B/XIAP 轴促进细胞凋亡，使结肠癌细胞对 5-氟尿嘧啶重新敏感
DOI：
10.1038/s41598-017-04172-z
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发表时间：
2017-06-23
影响因子：
4.6
通讯作者：
Zhang Y
中科院分区：
文献类型：
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作者：
Zhao C;Zhao Q;Zhang C;Wang G;Yao Y;Huang X;Zhan F;Zhu Y;Shi J;Chen J;Yan F;Zhang Y
耐药与细胞凋亡失衡密切相关，无论用何种治疗方法，耐药都赋予结直肠癌（CRC）增强的进展能力。我们报告说，miR-15 b-5 p是一种肿瘤抑制因子，其水平在CRC细胞和组织中总体下降。miR-15 b-5 p的过表达不仅能促进5-FU诱导的细胞凋亡，而且能逆转5-FU的体内外耐药性。miR-15 B-5 p作为炎症诱导的肿瘤的关键介质，其增强这些治疗作用主要归因于通过负调控NF-κB1及其激酶复合物之一IKK-α靶向NF-κB信号通路。miR-15 b-5 p通过靶向抗凋亡蛋白XIAP介导体外NF-κ B调节。总之，这些结果建立了miR-15 b介导的细胞凋亡调节轴，其逆转化疗耐药性并抑制CRC进展。这些发现表明miR-15 b-5 p可能是治疗CRC的潜在药物，特别是对于5-FU耐药的CRC。
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.