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FTO promotes the progression of cervical cancer by regulating the N6-methyladenosine modification of ZEB1 and Myc
Authors:Aihong Wang  Canhui Jin  Ying Wang  Juanjuan Yu  Ruifang Wang  Xiaoyu Tian
Institution:1. Department of Gynaecology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China

Department of Gynecologic and Obstetrics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan Province, China;2. Department of Gynaecology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China

Department of Gastrointestinal Tumor Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan Province, China;3. Department of Gynaecology, South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China;4. Department of Gynecologic and Obstetrics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan Province, China

Abstract:Cervical cancer is a malignant tumor of the cervix in women. However, the pathogenesis of cervical cancer has not been fully understood. N6-methyladenosine (m6A) is a kind of RNA modification that plays a critical role in cancer development. We aim to find out the possible m6A regulatory mechanism of the fat mass and obesity-associated protein (FTO) on the development of cervical cancer. The proliferative capacity of cervical cancer cells was detected by 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyl-2H-tetrazolium bromide (MTT), colony formation and 5-ethynyl-20-deoxyuridine (EdU) staining. The migration and invasion of cervical cancer cells were determined by transwell assay. The function of FTO on tumor growth was evaluated by a xenograft model. We found that FTO was highly expressed in cervical cancer tissues and cell lines. FTO silencing suppressed the proliferation, migration, and invasion of cervical cancer cells. Mechanistically, FTO modulated the m6A modification of Zinc finger E-box binding homeobox 1 (ZEB1) and Myelocytomatosis oncogene (Myc). Furthermore, ZEB1 and Myc overexpression reverse the effect of FTO knockdown on the malignant behaviors of cervical cancer cells. FTO may be a novel therapeutic target for cervical cancer.
Keywords:cervical carcinoma  FTO  m6A  Myc  ZEB1
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