Thyroid hormone suppresses cell proliferation through endoglin-mediated promotion of p21 stability

Y-H Lin1, Y-H Huang, M-H Wu

  • 1Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, Republic of China.

Oncogene
|February 5, 2013
PubMed

Insights

Thyroid hormone (T3) signaling suppresses hepatocellular carcinoma (HCC) cell proliferation by upregulating endoglin. This mechanism involves T3/TR signaling influencing p21 stability, with endoglin acting as a tumor suppressor in HCC.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Hypothyroidism is linked to increased hepatocellular carcinoma (HCC) risk, but mechanisms are unclear.
  • Thyroid hormone (T3) and its receptor (TR) regulate metabolism and growth.
  • Endoglin is a potential T3/TR target gene implicated in T3 regulation.

Purpose of the Study:

  • To investigate the role of T3/TR signaling in HCC.
  • To elucidate the function of endoglin in T3-mediated regulation of HCC cell proliferation.

Main Methods:

  • In vitro and in vivo experiments to assess T3 regulation of endoglin.
  • Electrophoretic mobility shift and chromatin immunoprecipitation assays to identify thyroid hormone response elements in the endoglin promoter.
  • Analysis of endoglin expression in HCC patient subgroups and correlation with histology and TRα1.
  • Experiments involving endoglin knockdown in HCC cells to assess proliferation and p21 polyubiquitination.

Main Results:

  • T3 positively regulates endoglin mRNA and protein levels.
  • Endoglin promoter contains T3/TR binding sites.
  • Endoglin is downregulated in HCC and associated with histology grade and TRα1 expression.
  • T3-mediated suppression of HCC cell proliferation involves p21.
  • Endoglin knockdown promotes HCC cell proliferation by affecting p21 stability.

Conclusions:

  • T3/TR signaling suppresses HCC cell proliferation via endoglin upregulation.
  • Endoglin influences p21 stability, contributing to its tumor suppressor role in HCC.
  • Endoglin acts as an inhibitor of cell proliferation in HCC cell lines.

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