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

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.

• Authors: 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-Ming Tsai, Ching-Ying Chen, Tina P Lin, Yung-Hsin Yeh, Wei-Jan Chen, Kwang-Huei Lin
• Journal: Journal of hepatology (J Hepatol) Vol. 62 Issue 6 Pg. 1328-40 (Jun 2015) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 25617495 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• IRF1 protein, human
• Interferon Regulatory Factor-1
• MIRN130 microRNA, human
• MicroRNAs
• Receptors, Thyroid Hormone
• Triiodothyronine

Topics

• Aged
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics, physiology)
• Disease Progression
• Down-Regulation
• Epithelial-Mesenchymal Transition
• Female
• Hep G2 Cells
• Humans
• Interferon Regulatory Factor-1 (genetics, metabolism)
• Liver Neoplasms (genetics, metabolism, pathology)
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Invasiveness (genetics, pathology, physiopathology)
• Receptors, Thyroid Hormone (metabolism)
• Signal Transduction
• Triiodothyronine (metabolism)