MicroRNA-657 promotes tumorigenesis in hepatocellular carcinoma by targeting transducin-like enhancer protein 1 through nuclear factor kappa B pathways

Hepatology. 2013 May;57(5):1919-30. doi: 10.1002/hep.26162. Epub 2013 Apr 5.

Abstract

Growing evidence indicates that deregulation of microRNAs (miRNAs) contributes to tumorigenesis. Dysregulation of miR-657 has been observed in several types of cancers, but its biological function is still largely unknown. Our results showed that miR-657 expression can be induced by hepatitis viral proteins and is significantly increased in hepatocellular carcinoma (HCC) tissues. Moreover, introduction of miR-657 dramatically increases proliferation and colony formation of HCC cells in vitro and induces tumor development in immunodeficient mice. Further studies showed that miR-657 directly targets the transducin-like enhancer protein 1 (TLE1) 3' untranslated region (UTR) and activates nuclear factor kappa B (NF-κB) pathways that contribute to hepatocarcinogenesis.

Conclusion: This study identified a mechanism whereby miRNA-657 contributed to HCC through novel cancer pathways and provides new insights into the potential molecular mechanisms of hepatic carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism*
  • Cells, Cultured
  • Co-Repressor Proteins
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • In Vitro Techniques
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • NF-kappa B / metabolism*
  • Repressor Proteins / metabolism*
  • Signal Transduction / physiology*
  • Transfection
  • Transplantation, Heterologous

Substances

  • Co-Repressor Proteins
  • MIRN657 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Repressor Proteins
  • TLE1 protein, human