title: miR-483-5p determines mitochondrial fission and cisplatin sensitivity in tongue squamous cell carcinoma by targeting FIS1.
abstract: 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.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Song
authors.initials: S
authors.lastname: Fan
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Wei-Xiong
authors.initials: WX
authors.lastname: Chen
authors.affiliation: Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Xiao-Bin
authors.initials: XB
authors.lastname: Lv
authors.affiliation: Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China.
authors.forename: Qiong-Lan
authors.initials: QL
authors.lastname: Tang
authors.affiliation: Department of Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Sun
authors.affiliation: Department of Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Bo-Du
authors.initials: BD
authors.lastname: Liu
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Jiang-Long
authors.initials: JL
authors.lastname: Zhong
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Zhao-Yu
authors.initials: ZY
authors.lastname: Lin
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: You-Yuan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Qun-Xing
authors.initials: QX
authors.lastname: Li
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Han-Qing
authors.initials: HQ
authors.lastname: Zhang
authors.affiliation: Xaverian Brothers High School, Westwood, MA 02090, United States.
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Li
authors.affiliation: Department of Pathology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637600, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wen
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Wei-Liang
authors.initials: WL
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China; Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: lijinsong1967@163.com.
authors.forename: Jin-Song
authors.initials: JS
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C476525:FIS1 protein, human; C548912:MIRN483 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins; D002945:Cisplatin
keywords: Cisplatin sensitivity; FIS1; Mitochondrial fission; Tongue squamous cell carcinoma; miR-483-5p