Transcription factor FOXA3 promotes the development of Hepatoblastoma via regulating HNF1A, AFP, and ZFHX3 expression

J Clin Lab Anal. 2021 Mar;35(3):e23686. doi: 10.1002/jcla.23686. Epub 2020 Dec 24.

Abstract

Objective: In this research paper, we aimed to study the role of FOXA3 in hepatoblastoma (HB) and the molecular mechanism.

Methods: Immunohistochemistry was applied to determine the expression situation of FOXA3 and AFP in HB tissues and the adjacent normal tissues. FOXA3, HNF1A, and ZFHX3 expressions in HB tissues and the normal tissues were measured by Western blot. HB cell lines were randomly divided into 4 groups: Model, si-NC, si-FOXA3-1, and si-FOXA3-2 group. The HB cell viability and colony formation characteristics in the 4 groups were explored by CCK-8 and cell cloning formation assay, respectively. The expression of FOXA3, AFP, HNF1A, ZFHX3, and MYC in HB cells after knockdown of FOXA3 was measured.

Results: FOXA3, AFP, and HNF1A expressions were significantly up-regulated in HB tissues, while ZFHX3 expression was down-regulated. Knockdown of FOXA3 markedly inhibited HB cell viability and cloning formation ability. Knockdown of FOXA3 decreased FOXA3, AFP, and HNF1A/MYC expression, while increased ZFHX3 expression.

Conclusion: FOXA3 promotes the occurrence and development of HB by up-regulating AFP and HNF1A/MYC expression, and down-regulating ZFHX3 expression.

Keywords: AFP; FOXA3; HNF1A; hepatoblastoma; transcription.

MeSH terms

  • Cell Survival
  • Child, Preschool
  • Female
  • Hepatoblastoma / genetics
  • Hepatoblastoma / metabolism
  • Hepatoblastoma / pathology*
  • Hepatocyte Nuclear Factor 1-alpha / metabolism
  • Hepatocyte Nuclear Factor 3-gamma / genetics
  • Hepatocyte Nuclear Factor 3-gamma / metabolism*
  • Homeodomain Proteins / metabolism
  • Humans
  • Infant
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • alpha-Fetoproteins / metabolism*

Substances

  • AFP protein, human
  • FOXA3 protein, human
  • HNF1A protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • Homeodomain Proteins
  • alpha-Fetoproteins
  • Hepatocyte Nuclear Factor 3-gamma
  • ZFHX3 protein, human