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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4509-4518
Number of pages10
JournalOncogene
Volume32
Issue number38
DOIs
Publication statusPublished - Sep 19 2013
Externally publishedYes

Fingerprint

Thyroid Hormone Receptors
Hepatocellular Carcinoma
Neoplasm Metastasis
Neoplasms
MicroRNAs
Cell Movement
Matrix Metalloproteinase 3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Chromatin Immunoprecipitation
Luciferases
Thyroid Hormones
Survival
Growth
Genes

Keywords

  • hepatocellular carcinoma
  • matrix metalloproteinases-3
  • microRNA
  • p-AKT
  • thyroid hormone

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Lin, Y. H., Liao, C. J., Huang, Y. H., Wu, M. H., Chi, H. C., Wu, S. M., ... 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

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

In: Oncogene, Vol. 32, No. 38, 19.09.2013, p. 4509-4518.

Research output: Contribution to journalArticle

Lin, YH, Liao, CJ, Huang, YH, Wu, MH, Chi, HC, Wu, SM, Chen, CY, Tseng, YH, Tsai, CY, Chung, IH, Wu, TI, Tsai, MM, Lin, CD & Lin, KH 2013, 'Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells', Oncogene, vol. 32, no. 38, pp. 4509-4518. https://doi.org/10.1038/onc.2013.309
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. / Thyroid hormone receptor represses miR-17 expression to enhance tumor metastasis in human hepatoma cells. In: Oncogene. 2013 ; Vol. 32, No. 38. pp. 4509-4518.
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abstract = "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.",
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AU - Wu, S. M.

AU - Chen, C. Y.

AU - Tseng, Y. H.

AU - Tsai, C. Y.

AU - Chung, I. H.

AU - Wu, T. I.

AU - Tsai, M. M.

AU - Lin, C. D.

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