MiR-1180 promotes apoptotic resistance to human hepatocellular carcinoma via activation of NF-κB signaling pathway.
MiR-1180 promotes apoptotic resistance to human hepatocellular carcinoma via activation of NF-κB signaling pathway.
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DOI：
10.1038/srep22328
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发表时间：
2016-03-01
影响因子：
4.6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Tan G;Wu L;Tan J;Zhang B;Tai WC;Xiong S;Chen W;Yang J;Li H
细胞凋亡抵抗是人肝细胞癌发生发展的重要因素。因此，了解细胞凋亡抵抗的分子机制对于开发抗癌药物至关重要。重要的是，小的非编码microRNAs(MiRNAs)已被报道为检测肿瘤发生和发展的关键生物标记物。在本研究中，我们证明miR-1180在肝细胞癌中表达上调。异位表达miR-1180在肝癌中具有抗凋亡作用，而抑制miR-1180在体外和体内都增加了细胞的凋亡。此外，我们的结果表明，miR-1180通过转录后下调直接靶向核因子-κB信号通路的关键抑制物(即OTUD7B和TNIP2)和促凋亡的Bcl2相关死亡启动子(BAD)蛋白。因此，MIR1180在肝癌中的抗凋亡作用可能是通过下调其负调控因子而激活NF-κB途径实现的。总之，我们的研究揭示了miR-1180在肝癌细胞凋亡抵抗中的关键作用。
Apoptosis resistance in human hepatocellular carcinoma (HCC) is a significant factor in carcinogenesis. Therefore, understanding the molecular mechanisms involved in apoptosis resistance is crucial for developing anticancer therapies. Importantly, small non-coding microRNAs (miRNAs) have been reported as key biomarkers for detecting tumour onset and progression. In the present study, we demonstrate that miR-1180 is upregulated in HCC. Ectopic expression of miR-1180 has an anti-apoptotic effect in HCC, while miR-1180 inhibition increases cell apoptosis, both in vitro and in vivo. Moreover, our results show that miR-1180 directly targets key inhibitors of the nuclear factor (NF)-κB signaling pathway (i.e., OTUD7B and TNIP2) and the pro-apoptotic Bcl-2 associated death promoter (BAD) protein by post-transcriptional downregulation. Therefore, the anti-apoptotic function of miR-1180 in HCC may occur through NF-κB pathway activation via downregulation of its negative regulators. In conclusion, our study reveals the critical role of miR-1180 during apoptosis resistance in HCC.