Nuclear FOXP3 inhibits tumor growth and induced apoptosis in hepatocellular carcinoma by targeting c-Myc

Zhongqin Gong1, Hao Jia1,2, Jianqing Yu1

  • 1Department of Surgery, Faculty of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Oncogenesis
|October 29, 2020
PubMed

Insights

FOXP3 acts as a tumor suppressor in hepatocellular carcinoma (HCC). High FOXP3 expression inhibits HCC growth by suppressing c-Myc, improving patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • The role of FOXP3 and its isoforms in hepatocellular carcinoma (HCC) remains unclear.
  • Investigating FOXP3 expression and function is crucial for understanding HCC progression.

Purpose of the Study:

  • To investigate the expression and function of FOXP3 and its isoforms in HCC.
  • To determine the correlation between FOXP3 levels and clinicopathologic characteristics in HCC patients.

Main Methods:

  • Nested PCR, quantitative real-time PCR, and immunohistochemistry (IHC) were used to determine FOXP3 and isoform levels.
  • Functional assays included immunofluorescence, luciferase assay, co-immunoprecipitation, and chromatin immunoprecipitation (ChIP).
  • A mouse tumor model was utilized for in vivo validation.

Main Results:

  • FOXP3 and FOXP3Δ3 were identified as major isoforms in HCC; FOXP3Δ3 levels did not differ significantly between tumor and normal tissues.
  • High FOXP3 protein expression correlated with good overall survival and significantly reduced HCC cell proliferation, migration, and invasion.
  • FOXP3, through nuclear translocation, synergistically inhibited the oncogene c-Myc with Smad2/3/4 by binding to the c-Myc promoter.

Conclusions:

  • FOXP3 functions as a tumor suppressor in HCC.
  • FOXP3 inhibits HCC growth by directly or indirectly suppressing c-Myc, potentially through interaction with Smad2/3/4.
  • High FOXP3 expression is associated with improved survival in HCC patients.

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