MicroRNA-1/206 Targets c-Met and Inhibits Rhabdomyosarcoma Development

J Biol Chem. 2009 Oct 23;284(43):29596-604. doi: 10.1074/jbc.M109.020511. Epub 2009 Aug 26.

Abstract

MicroRNAs (miRNAs) are endogenous short (approximately 22) nucleotide RNAs that regulate gene function by modification of target mRNAs. miRNA-1 (miR-1) and miRNA-206 (miR-206) are highly expressed in skeletal muscle. Due to the tissue-specific nature of miR-1/206 for skeletal muscles, we investigated the role of miR-1/206 in the development of rhabdomyosarcoma. Initially, we demonstrated that miR-1/206 expression was suppressed in rhabdomyosarcomas and found at very low levels in a rhabdomyosarcoma RD cell line. Transient transfection of miR-1/206 into cultured RD cells led to a significant decrease in cell growth and migration. Using bioinformatics, we identified two putative miR-1/206 binding sites within the 3'-untranslated region of the human c-Met mRNA. miR-1/206 was then shown to have activity on mRNA expression by targeting the c-Met 3'-untranslated region. The expression of c-Met protein was shown to be down-regulated by subsequent Western blot analysis. Conversely, up-regulation of c-Met was confirmed in tissue samples of human rhabdomyosarcoma, with its level inversely correlated with miR-1/206 expression. In vivo, miR-1/206-expressing tumor cells showed growth delay in comparison with negative control. Our results demonstrated that miR-1/206 suppressed c-Met expression in rhabdomyosarcoma and could function as a potent tumor suppressor in c-Met-overexpressing tumors. Inhibition of miR-1/206 function could contribute to aberrant cell proliferation and migration, leading to rhabdomyosarcoma development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • 3' Untranslated Regions / metabolism
  • Animals
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Muscle, Skeletal / metabolism
  • Neoplasm Transplantation
  • Organ Specificity
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Rhabdomyosarcoma / metabolism*
  • Transfection
  • Transplantation, Heterologous

Substances

  • 3' Untranslated Regions
  • MIRN1 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-met