Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells

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

研究成果: Article

29 引文 斯高帕斯(Scopus)

摘要

MicroRNAs (miRNAs) are thought to control tumor metastasis through direct interactions with target genes. Thyroid hormone (T 3) and its receptor (TR) are involved in cell growth and cancer progression. However, the issue of whether miRNAs participate in T 3 /TR-mediated tumor migration is yet to be established. In the current study, we demonstrated that T 3 /TR negatively regulates mature miR-17 transcript expression, both in vitro and in vivo. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays localized the regions responding to TR-mediated repression to positions -2234/-2000 of the miR-17 promoter sequence. Overexpression of miR-17 markedly inhibited cell migration and invasion in vitro and in vivo, mediated via suppression of matrix metalloproteinases (MMP)-3. Moreover, p-AKT expression was increased in miR-17-knockdown cells that led to enhanced cell invasion, which was blocked by LY294002. Notably, low miR-17 expression was evident in highly metastatic cells. The cell migration ability was increased by T 3, but partially reduced upon miR-17 overexpression. Notably, TRα1 was frequently upregulated in hepatocellular carcinoma (HCC) samples and associated with low overall survival (P=0.023). miR-17 expression was significantly negatively associated with TRα1 (P=0.033) and MMP3 (P=0.043) in HCC specimens. Data from our study suggest that T 3 /TR, miR-17, p-AKT and MMP3 activities are interlinked in the regulation of cancer cell metastasis.

原文English
頁(從 - 到)4509-4518
頁數10
期刊Oncogene
32
發行號38
DOIs
出版狀態Published - 2013 九月 19

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Lin, Y. H., Liao, C. J., Huang, Y. H., Wu, M. H., Chi, H. C., Wu, S. M., Chen, C. Y., Tseng, Y. H., Tsai, C. Y., Chung, I. H., Wu, T. I., Tsai, M. M., Lin, C. D., & Lin, K. H. (2013). Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells. Oncogene, 32(38), 4509-4518. https://doi.org/10.1038/onc.2013.309