Zhou Liang, Gao Ruirui, Wang Yinghui, Zhou Meijuan, Ding Zhenhua
Department of Radiation Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Int J Mol Sci. 2017 May 30;18(6):1157. doi: 10.3390/ijms18061157.
Pro-apoptotic BCL2 associated X (BAX) is traditionally thought to be regulated by anti-apoptotic BCL-2 family members, like BCL2-like 1 (BCL-XL), at the protein level. However, the posttranscriptional regulation of BAX is under explored. In this study, we identified BAX as the novel downstream target of miR-365, which is supported by gain- and loss-of-function studies of onco-miR-365. Loss of BAX by either RNA interference or highly-expressed miR-365 in cells of cutaneous squamous cell carcinoma (CSCC) enhanced the tumor resistance against apoptosis, while repressing cell proliferation, migration, and invasiveness. In vivo experiment confirmed that BAX knockdown promotes the growth of CSCC xenografts. Collectively, our results find a miR-365-BAX axis for alleviating the pro-apoptotic effects of BAX, which promotes CSCC development and may facilitate the generation of novel therapeutic regimens to the clinical treatment of CSCC.
传统上认为，促凋亡蛋白BCL2相关X蛋白（BAX）在蛋白质水平上受抗凋亡BCL-2家族成员（如BCL2样蛋白1，即BCL-XL）的调控。然而，BAX的转录后调控仍有待探索。在本研究中，我们确定BAX是miR-365的新型下游靶点，这一结论得到了癌基因miR-365功能获得和功能缺失研究的支持。在皮肤鳞状细胞癌（CSCC）细胞中，通过RNA干扰或高表达miR-365使BAX缺失，增强了肿瘤对凋亡的抗性，同时抑制了细胞增殖、迁移和侵袭能力。体内实验证实，BAX基因敲低促进了CSCC异种移植瘤的生长。总体而言，我们的研究结果发现了一个miR-365-BAX轴，该轴可减轻BAX的促凋亡作用，促进CSCC的发展，并可能有助于为CSCC的临床治疗制定新的治疗方案。
