title: Repression of microRNA-130b by thyroid hormone enhances cell motility.
abstract: OBJECTIVE
  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.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Meng-Han
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Liao
authors.affiliation: Liver Research Center, Department of Hepato-Gastroenterology, Chang-Gung Memorial Hospital, Linkou, Taoyuan 333, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Department of Medical Research, Mackay Memorial Hospital, Taipei 251, Taiwan.
authors.forename: Cheng-Yi
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Yi-Hsin
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: I-Hsiao
authors.initials: IH
authors.lastname: Chung
authors.affiliation: Department of Nursing, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Tsai
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan.
authors.forename: Ching-Ying
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Pre-med Program, Pacific Union College, Angwin 94508, USA.
authors.forename: Tina P
authors.initials: TP
authors.lastname: Lin
authors.affiliation: Division of Cardiology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 333, Taiwan.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Yeh
authors.affiliation: Division of Cardiology, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 333, Taiwan.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan 333, Taiwan. Electronic address: khlin@mail.cgu.edu.tw.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics* / Q000502:physiology*; D018450:Disease Progression; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015398:Signal Transduction; D014284:Triiodothyronine / Q000378:metabolism*
chemical_list: C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine
keywords: Hepatocellular carcinoma; IRF1; Metastasis; Thyroid hormone; miR-130b