Hepatocyte nuclear factor 4α suppresses the aggravation of colon carcinoma

Hou Shan Yao1, Juan Wang1, Xiao Ping Zhang2

  • 1Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai, China.

Insights

Hepatocyte nuclear factor 4-α (HNF4α) is downregulated in colon cancer, correlating with worse survival. Restoring HNF4α inhibits tumor growth, metastasis, and promotes apoptosis by affecting EMT and cell cycle progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hepatocyte nuclear factor 4-α (HNF4α) is a nuclear receptor.
  • HNF4α is expressed at lower levels in colon carcinoma tissues.
  • The role of HNF4α in colon cancer progression is unclear.

Purpose of the Study:

  • To investigate the role of HNF4α in colon carcinoma progression.
  • To elucidate the molecular mechanisms underlying HNF4α's function in colon cancer.

Main Methods:

  • Analysis of HNF4α expression in colon carcinoma specimens.
  • Correlation of HNF4α expression with clinical parameters and patient survival.
  • In vitro studies using colon carcinoma cell lines (HT29, LoVo, SW480) with ectopic HNF4α expression.
  • In vivo studies using xenograft models.
  • Analysis of epithelial-mesenchymal transition (EMT) markers and signaling pathways (Wnt/β-catenin).

Main Results:

  • HNF4α mRNA and protein were significantly downregulated in colon carcinoma tissues.
  • Low HNF4α expression correlated with advanced pT classification, lymph node metastasis, distant metastasis, and clinical stage.
  • Patients with low HNF4α expression had significantly worse progression-free survival (PFS) and overall survival (OS).
  • Ectopic HNF4α expression inhibited colon cancer cell proliferation, migration, invasion, induced G2/M phase arrest, promoted apoptosis, and upregulated E-cadherin while downregulating vimentin.
  • HNF4α overexpression suppressed tumor growth and liver metastasis in vivo, downregulated snail, slug, and twist, and inhibited EMT via the Wnt/β-catenin pathway.
  • HNF4α downregulation may be mediated by promoter methylation.

Conclusions:

  • Downregulation of HNF4α plays a critical role in colon carcinoma progression.
  • HNF4α acts as a tumor suppressor in colon cancer.
  • HNF4α inhibits EMT, apoptosis, and cell cycle progression, potentially through the Wnt/β-catenin pathway.
  • HNF4α may serve as a prognostic biomarker for colon cancer.

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