HNF4A Regulates the Proliferation and Tumor Formation of Cervical Cancer Cells through the Wnt/ β-Catenin Pathway

Oxid Med Cell Longev. 2022 Jan 28:2022:8168988. doi: 10.1155/2022/8168988. eCollection 2022.

Abstract

Hepatocyte nuclear factor 4 alpha (HNF4A) is a transcriptional factor which plays an important role in the development of the liver, kidney, and intestines. Nevertheless, its role in cervical cancer and the underlying mechanism remain unknown. In this study, both immunohistochemistry and western blotting revealed that the expression of HNF4A was downregulated in cervical cancer. Xenograft assays suggested that HN4A could inhibit tumorigenic potential of cervical cancer in vivo. Functional studies illustrated that HNF4A also inhibited the proliferation and viability of cervical cancer cells in vitro. In addition, FACS analysis implied that HNF4A could induce cell cycle arrest from the G0/G1 phase to S phase. Further studies suggested that HNF4A downregulated the activity of the Wnt/β-catenin pathway. Altogether, our data demonstrated that HNF4A inhibited tumor formation and proliferation of cervical cancer cells through suppressing the activity of the Wnt/β-catenin pathway.

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism*
  • Case-Control Studies
  • Cell Cycle Checkpoints / genetics
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HeLa Cells
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Humans
  • Mice
  • Mice, Nude
  • Transfection
  • Tumor Burden / genetics
  • Up-Regulation / genetics
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway / genetics*
  • Xenograft Model Antitumor Assays
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Wnt Proteins
  • beta Catenin