title: Thyroid hormone suppresses expression of stathmin and associated tumor growth in hepatocellular carcinoma.
abstract: 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 T3significantly 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, T3regulation 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 T3in the liver. This T3-mediated suppression of STMN1 supports the theory that T3plays an inhibitory role in HCC tumor growth, and suggests that the lack of normal THR function leads to elevated STMN1 expression and malignant growth.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Division of Neurosurgery, Chang Gung Memorial Hospital-Linkou &Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Tzu-Kang
authors.initials: TK
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Nursing, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Chang
authors.affiliation: Molecular Medicine Research Center, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: First Cardiovascular Division, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan, Republic of China.|Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan 333, Taiwan, Republic of China.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000502:physiology*; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D011988:Receptors, Thyroid Hormone / Q000502:physiology; D050777:Stathmin / Q000235:genetics*; D014284:Triiodothyronine / Q000502:physiology*
chemical_list: D011988:Receptors, Thyroid Hormone; C493995:STMN1 protein, human; D050777:Stathmin; D014284:Triiodothyronine