miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1
miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1
复制标题
miR-483-5p 通过靶向 FIS1 来确定舌鳞状细胞癌中的线粒体裂变和顺铂敏感性。
DOI：
10.1016/j.canlet.2015.03.045
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发表时间：
2015-07-01
期刊：
影响因子：
9.7
通讯作者：
Li, Jin-Song
中科院分区：
文献类型：
--
作者：
Fan, Song;Chen, Wei-Xiong;Li, Jin-Song
线粒体在启动细胞凋亡中起着重要作用。然而，顺铂是否可以通过启动线粒体分裂途径来诱导细胞凋亡，以及这种作用的机制仍不清楚。在这项研究中，我们发现在顺铂作用下，舌鳞状细胞癌(TSCC)细胞中线粒体分裂蛋白FIS1表达上调。FIS1基因敲除可减弱线粒体分裂和顺铂敏感性。我们发现FIS1是miR-483-5p的直接靶点，并且miR-483-5p在体外和体内都能抑制线粒体分裂和顺铂敏感性。此外，在多中心的回顾性分析中，我们发现miR-483-5p和FIS1与顺铂敏感性和TSCC患者的总体生存率显著相关。本研究揭示了由miR-483-5p和FIS1组成的新的线粒体分裂途径调节顺铂的敏感性。MiR-483-5p和FIS1水平的调节可能为提高顺铂的敏感性提供新的途径。(C)2015爱思唯尔爱尔兰有限公司。保留所有权利。
Mitochondria play an important role in the initiation of apoptosis. However, whether cisplatin can induce apoptosis by initiating a mitochondrial fission pathway and the mechanism underlying this effect remain poorly understood. In this study, we show that the mitochondrial fission protein FIS1 is upregulated upon cisplatin treatment in tongue squamous cell carcinoma (TSCC) cells. FIS1 knockdown can attenuate mitochondrial fission and cisplatin sensitivity. We found that FIS1 is a direct target of miR-483-5p and that miR-483-5p can inhibit mitochondrial fission and cisplatin sensitivity in vitro and in vivo. Furthermore, we found that miR-483-5p and FIS1 are significantly associated with cisplatin sensitivity and with overall survival in patients with TSCC in a retrospective analysis of multiple centers. This study revealed that a novel mitochondrial fission pathway composed of miR-483-5p and FIS1 regulates cisplatin sensitivity. The modulation of miR-483-5p and FIS1 levels may provide a new approach for increasing cisplatin sensitivity. (C) 2015 Elsevier Ireland Ltd. All rights reserved.