Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, 150000, China.
Translation Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150000, China.
Sci Rep. 2017 Jun 23;7(1):4194. doi: 10.1038/s41598-017-04172-z.
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.
耐药性与细胞凋亡失衡密切相关，使结直肠癌（CRC）即使在接受治疗的情况下也具有更强的进展能力。我们报告 miR-15b-5p 是一种肿瘤抑制因子，其水平在 CRC 细胞和组织中普遍降低。miR-15b-5p 的过表达不仅促进了 5-氟尿嘧啶（5-FU）诱导的细胞凋亡，而且还在体外和体内逆转了 5-FU 的化疗耐药性。作为炎症诱导癌症的关键介质，miR-15b-5p 通过负调控 NF-κB1 和其激酶复合物 IKK-α 来增强这些治疗效果，主要归因于靶向 NF-κB 信号通路。miR-15b-5p 通过靶向体外抗凋亡蛋白 XIAP 来介导 NF-ĸB 调节。总之，这些结果确立了 miR-15b 介导的细胞凋亡调节轴，该轴可逆转化疗耐药性并抑制 CRC 的进展。这些发现表明，miR-15b-5p 可能是 CRC 治疗的一种潜在药物，特别是对 5-FU 耐药的 CRC。
