FTO promotes the progression of cervical cancer by regulating the N6-methyladenosine modification of ZEB1 and Myc

Mol Carcinog. 2023 Aug;62(8):1228-1237. doi: 10.1002/mc.23559. Epub 2023 Jun 12.

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: FTO; Myc; ZEB1; cervical carcinoma; m6A.

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Cell Line
  • Cell Line, Tumor
  • Female
  • Humans
  • Oncogenes
  • Uterine Cervical Neoplasms* / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics

Substances

  • Zinc Finger E-box-Binding Homeobox 1
  • ZEB1 protein, human
  • FTO protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO