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GATA3 is downregulated in HCC and accelerates HCC aggressiveness by transcriptionally inhibiting slug expression

Zhuoliang Zhang1, Xingliang Fang1, Guilin Xie1

  • 1Department of General Surgery I, The Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China.

Oncology Letters
|February 22, 2021
PubMed

Insights

GATA3 is downregulated in hepatocellular carcinoma (HCC), acting as a tumor suppressor. Low GATA3 expression correlates with poor prognosis, inhibiting cancer cell proliferation, migration, and invasion by regulating slug expression and suppressing epithelial-mesenchymal transition (EMT).

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • GATA3 (GATA Binding Protein 3) is frequently downregulated in various cancers, including gastric cancer and osteosarcoma.
  • Its role in hepatocellular carcinoma (HCC) development and progression remains to be fully elucidated.

Purpose of the Study:

  • To investigate the function of GATA3 as a potential tumor suppressor in hepatocellular carcinoma (HCC).
  • To explore the association between GATA3 expression and clinicopathological features, prognosis, and cellular behaviors in HCC patients.

Main Methods:

  • Analysis of GATA3 expression in 162 HCC tumor tissues and adjacent normal tissues.
  • Correlation analysis between GATA3 expression and clinicopathological parameters (tumor size, TNM stage, lymph node metastasis).
  • In vitro gain-of-function and loss-of-function assays in HCC cell lines; investigation of GATA3's effect on epithelial-mesenchymal transition (EMT) via slug expression.

Main Results:

  • GATA3 expression was significantly downregulated in HCC tissues compared to normal tissues.
  • Low GATA3 expression was associated with larger tumor size, advanced TNM stage, lymph node metastasis, and poorer patient survival.
  • Overexpression of GATA3 inhibited HCC cell proliferation, migration, and invasion, while GATA3 inhibition promoted these behaviors. GATA3 suppressed EMT by downregulating slug expression, and slug overexpression counteracted GATA3's inhibitory effects.

Conclusions:

  • GATA3 functions as a tumor suppressor in HCC, with its downregulation correlating with aggressive tumor characteristics and poor outcomes.
  • GATA3 inhibits HCC cell proliferation, migration, and invasion, partly through the transcriptional suppression of slug, thereby inhibiting EMT.
Keywords:
GATA3epithelial-mesenchymal transitioninvasionmigrationproliferation

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