Repression of microRNA-130b by thyroid hormone enhances cell motility

Yang Hsiang Lin, Meng Han Wu, Chia Jung Liao, Ya Hui Huang, Hsiang Cheng Chi, Sheng Ming Wu, Cheng Yi Chen, Yi Hsin Tseng, Chung Ying Tsai, I. Hsiao Chung, Ming Chieh Tsai, Ching Ying Chen, Tina P. Lin, Yung Hsin Yeh, Wei Jan Chen, Kwang Huei Lin

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35 Citations (Scopus)

Abstract

Background & Aims Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. Although deregulation of microRNA (miRNA) expression has been detected in many tumor types, the mechanisms underlying functional impairment and specific involvement of miRNAs in tumor metastasis remain unclear. In the current study, we aimed to elucidate the involvement of deregulated miRNA-130b (miR-130b) and its target genes mediated by T3/TR in cancer progression. Methods Quantitative reverse transcription-PCR, luciferase and chromatin immunoprecipitation assays were performed to identify the miR-130b transcript and the mechanisms implicated in its regulation. The effects of miR-130b on hepatocellular carcinoma (HCC) invasion were further examined in vitro and in vivo. Clinical correlations among miR-130b, TRs and interferon regulatory factor 1 (IRF1) were examined in HCC samples using Spearman correlation analysis. Results Our experiments disclosed negative regulation of miR-130b expression by T3/TR. Overexpression of miR-130b led to marked inhibition of cell migration and invasion, which was mediated via suppression of IRF1. Cell migration ability was promoted by T3, but partially suppressed upon miR-130b overexpression. Furthermore, miR-130b suppressed expression of epithelial-mesenchymal transition (EMT)-related genes, matrix metalloproteinase-9, phosphorylated mammalian target of rapamycin (mTOR), p-ERK1/2, p-AKT and p-signal transducer and activator of transcription (STAT)-3. Notably, miR-130b was downregulated in hepatoma samples and its expression patterns were inversely correlated with those of TRα1 and IRF1. Conclusions Our data collectively highlight a novel pathway interlinking T3/TR, miR-130b, IRF1, the EMT-related genes, p-mTOR, p-STAT3 and the p-AKT cascade, which regulates the motility and invasion of hepatoma cells.

Original languageEnglish
Article number5511
Pages (from-to)1328-1340
Number of pages13
JournalJournal of Hepatology
Volume62
Issue number6
DOIs
Publication statusPublished - Jun 1 2015
Externally publishedYes

Keywords

  • Hepatocellular carcinoma
  • IRF1
  • Metastasis
  • miR-130b
  • Thyroid hormone

ASJC Scopus subject areas

  • Hepatology

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  • Cite this

    Lin, Y. H., Wu, M. H., Liao, C. J., Huang, Y. H., Chi, H. C., Wu, S. M., Chen, C. Y., Tseng, Y. H., Tsai, C. Y., Chung, I. H., Tsai, M. C., Chen, C. Y., Lin, T. P., Yeh, Y. H., Chen, W. J., & Lin, K. H. (2015). Repression of microRNA-130b by thyroid hormone enhances cell motility. Journal of Hepatology, 62(6), 1328-1340. [5511]. https://doi.org/10.1016/j.jhep.2014.12.035