miR-548ag functions as an oncogene by suppressing MOB1B in the development of obesity-related endometrial cancer

Cancer Sci. 2023 Apr;114(4):1507-1518. doi: 10.1111/cas.15679. Epub 2022 Dec 23.

Abstract

Obesity is a high-risk factor in the development of endometrial cancer (EC). Our previous study observed that miR-548ag was significantly overexpressed in the sera of obese individuals. Here, we report the function of miR-548ag and its mechanism in promoting the obesity-related progression of EC. The content of miR-548ag was increased in the serum of obese EC individuals. Bioinformatics analysis indicated that the survival rate of EC patients with a higher expression of miR-548ag was significantly reduced. The Mps One Binder Kinase Activator 1B (MOB1B, the core member of the Hippo signaling pathway) is a direct target gene of miR-548ag, which is inversely correlated with the expression of miR-548ag. The overexpression of miR-548ag enhances the proliferation, invasion, and migration, and inhibits apoptosis by downregulating the expression of MOB1B, leading to the deactivation of the Hippo pathway in EC cell lines and contributing to tumor progression in vivo. Our study has established that miR-548ag functions as an oncogene by suppressing MOB1B in the development of obesity-related EC.

Keywords: Hippo pathway; MOB1B; endometrial cancer; miR-548ag; obesity.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Endometrial Neoplasms* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Obesity / complications
  • Obesity / genetics
  • Oncogenes / genetics

Substances

  • MicroRNAs