miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.
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.
['Fan|Song|S|', 'Chen|Wei-Xiong|WX|', 'Lv|Xiao-Bin|XB|', 'Tang|Qiong-Lan|QL|', 'Sun|Li-Juan|LJ|', 'Liu|Bo-Du|BD|', 'Zhong|Jiang-Long|JL|', 'Lin|Zhao-Yu|ZY|', 'Wang|You-Yuan|YY|', 'Li|Qun-Xing|QX|', 'Yu|Xin|X|', 'Zhang|Han-Qing|HQ|', 'Li|Yi-Lin|YL|', 'Wen|Bin|B|', 'Zhang|Zhang|Z|', 'Chen|Wei-Liang|WL|', 'Li|Jin-Song|JS|']
D000818:Animals D000970:Antineoplastic Agents D002294:Carcinoma, Squamous Cell D045744:Cell Line, Tumor D002945:Cisplatin D006258:Head and Neck Neoplasms D006801:Humans D008565:Membrane Proteins D051379:Mice D008807:Mice, Inbred BALB C D008819:Mice, Nude D035683:MicroRNAs D063154:Mitochondrial Dynamics D024101:Mitochondrial Proteins D000077195:Squamous Cell Carcinoma of Head and Neck D014062:Tongue Neoplasms D014162:Transfection D023041:Xenograft Model Antitumor Assays
miR-483-5p Mitochondrial fission Cisplatin sensitivity Tongue squamous cell carcinoma FIS1