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Thyroid hormone suppresses expression of stathmin and associated tumor growth in hepatocellular carcinoma

Yi-Hsin Tseng1, Ya-Hui Huang2, Tzu-Kang Lin3

  • 1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.

Scientific Reports
|December 10, 2016
PubMed

Insights

Thyroid hormone receptor (THR) suppresses the oncoprotein Stathmin (STMN1) in liver cancer. This mechanism inhibits hepatocellular carcinoma (HCC) growth, suggesting THR dysfunction promotes malignant growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Stathmin (STMN1) is an oncoprotein that promotes tumor growth and migration by disassembling microtubules.
  • The regulatory mechanisms of STMN1 expression in cancer remain largely unknown.
  • Thyroid hormone receptor (THR) is a nuclear receptor involved in various cellular processes.

Purpose of the Study:

  • To investigate the role of thyroid hormone receptor (THR) in the regulation of Stathmin (STMN1) expression.
  • To elucidate the molecular mechanisms by which THR affects hepatocellular carcinoma (HCC) progression.
  • To determine the therapeutic potential of targeting the THR-STMN1 axis in HCC.

Main Methods:

  • Analysis of STMN1 and THR expression in clinical HCC specimens.
  • Identification of STMN1 as a direct transcriptional target of THR in HepG2 cells.
  • Assessment of STMN1 knockdown effects on cell proliferation and tumor growth in vivo.
  • Investigation of STMN1's role in mediating T3-induced cell cycle arrest.

Main Results:

  • THR expression was negatively correlated with STMN1 expression in HCC.
  • Thyroid hormone (T3) significantly suppressed STMN1 mRNA and protein levels.
  • THR directly bound to the STMN1 promoter, inhibiting its transcriptional activity.
  • STMN1 knockdown reduced HCC cell proliferation and tumor growth.
  • Overexpression of STMN1 attenuated T3-mediated growth arrest and cell cycle regulation.

Conclusions:

  • The oncogene STMN1 is transcriptionally downregulated by T3 in liver cells.
  • T3-mediated suppression of STMN1 inhibits HCC tumor growth.
  • Dysfunctional THR signaling leads to elevated STMN1 and promotes malignant growth in the liver.

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