T3 has some interesting and, perhaps, surprising facets to its importance.
Please don't ask me to explain further! But if anyone can add to our ability to properly understand the paper, please do so.
Thyroid hormone suppresses expression of stathmin and associated tumor growth in hepatocellular carcinoma
Yi-Hsin Tseng, Ya-Hui Huang, Tzu-Kang Lin, Sheng-Ming Wu, Hsiang-Cheng Chi, Chung-Ying Tsai, Ming-Ming Tsai, Yang-Hsiang Lin, Wei-Chun Chang, Ya-Ting Chang, Wei-Jan Chen & Kwang-Huei Lin
Scientific Reports 6, Article number: 38756 (2016)
Received: 01 June 2016
Accepted: 14 November 2016
Published online: 09 December 2016
Stathmin (STMN1), a recognized oncoprotein upregulated in various solid tumors, promotes microtubule disassembly and modulates tumor growth and migration activity. However, the mechanisms underlying the genetic regulation of STMN1 have yet to be elucidated. In the current study, we report that thyroid hormone receptor (THR) expression is negatively correlated with STMN1 expression in a subset of clinical hepatocellular carcinoma (HCC) specimens. We further identified the STMN1 gene as a target of thyroid hormone (T3) in the HepG2 hepatoma cell line. An analysis of STMN1 expression profile and mechanism of transcriptional regulation revealed that T3 significantly suppressed STMN1 mRNA and protein expression, and further showed that THR directly targeted the STMN1 upstream element to regulate STMN1 transcriptional activity. Specific knockdown of STMN1 suppressed cell proliferation and xenograft tumor growth in mice. In addition, T3 regulation of cell growth arrest and cell cycle distribution were attenuated by overexpression of STMN1. Our results suggest that the oncogene STMN1 is transcriptionally downregulated by T3 in the liver. This T3-mediated suppression of STMN1 supports the theory that T3 plays an inhibitory role in HCC tumor growth, and suggests that the lack of normal THR function leads to elevated STMN1 expression and malignant growth.
Full paper freely available here:
For those who, like me, didn't really know what HCC is...
From Wikipedia, the free encyclopedia
Hepatocellular carcinoma (HCC), also called malignant hepatoma, is the most common type of liver cancer.