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

Y. H. Lin, Y. H. Huang, M. H. Wu, S. M. Wu, H. C. Chi, C. J. Liao, C. Y. Chen, Y. H. Tseng, C. Y. Tsai, M. M. Tsai, K. H. Lin

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25 引文 斯高帕斯(Scopus)

摘要

Hypothyroidism has been associated with significantly elevated risk for hepatocellular carcinoma (HCC), although the precise underlying mechanisms remain unknown at present. Thyroid hormone (T 3) and its receptor (TR) are involved in metabolism and growth. Endoglin is a T 3 /TR candidate target gene identified from our previous studies. Here, we demonstrated that T 3 positively regulates endoglin mRNA and protein levels, both in vitro and in vivo. The thyroid hormone response elements of endoglin were identified at positions -2114/-2004 and -2032/-1973 of the promoter region using the electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Endoglin was downregulated in the subgroups of HCC patients and significantly associated with histology grade (negative association, P=0.001), and this expression level was significantly associated with TRα1 in these HCC patients. Our results clearly indicate that p21 is involved in T 3 -mediated suppression of cell proliferation. Knock down of endoglin expression in HCC cells facilitated p21 polyubiquitination and promoted cell proliferation in the presence of T 3. The data collectively suggest that T 3 /TR signaling suppresses cell proliferation by upregulating endoglin, in turn, affecting p21 stability. The results indicate that endoglin has a suppressor role to inhibit cell proliferation in HCC cell lines.
原文英語
頁(從 - 到)3904-3914
頁數11
期刊Oncogene
32
發行號33
DOIs
出版狀態已發佈 - 8月 15 2013
對外發佈

ASJC Scopus subject areas

  • 分子生物學
  • 癌症研究
  • 遺傳學

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