miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells

Br J Cancer. 2015 Jul 14;113(2):252-8. doi: 10.1038/bjc.2015.170. Epub 2015 Jun 30.

Abstract

Background: The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC.

Methods: MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines).

Results: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and β-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1.

Conclusions: MicroRNA-9-3p was identified as the tumour-suppressor miR targetting TAZ expression in HCC cells.

MeSH terms

  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Liver Neoplasms / pathology*
  • MAP Kinase Signaling System
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-akt / physiology
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • beta Catenin / physiology

Substances

  • CTNNB1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN92 microRNA, human
  • MicroRNAs
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human
  • beta Catenin
  • Proto-Oncogene Proteins c-akt