miR-203, a tumor suppressor frequently down-regulated by promoter hypermethylation in rhabdomyosarcoma.

Journal Article (Clinical Trial;Journal Article)

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma found in children and young adults. It is characterized by the expression of a number of skeletal muscle-specific proteins, including MyoD and muscle α-actin. However, unlike normal myoblasts, RMS cells differentiate poorly both in vivo and in culture. As microRNAs are known to regulate tumorigenesis, intensive efforts have been made to identify microRNAs that are involved in RMS development. In this work, we found that miR-203 was frequently down-regulated by promoter hypermethylation in both RMS cell lines and RMS biopsies and could be reactivated by DNA-demethylating agents. Re-expression of miR-203 in RMS cells inhibited their migration and proliferation and promoted terminal myogenic differentiation. Mechanistically, miR-203 exerts its tumor-suppressive effect by directly targeting p63 and leukemia inhibitory factor receptor in RMS cells, which promotes myogenic differentiation by inhibiting the Notch and the JAK1/STAT1/STAT3 pathways, respectively. Our work reveals that miR-203 functions as a tumor suppressor in RMS development.

Full Text

Duke Authors

Cited Authors

  • Diao, Y; Guo, X; Jiang, L; Wang, G; Zhang, C; Wan, J; Jin, Y; Wu, Z

Published Date

  • January 3, 2014

Published In

Volume / Issue

  • 289 / 1

Start / End Page

  • 529 - 539

PubMed ID

  • 24247238

Pubmed Central ID

  • PMC3879574

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.494716


  • eng

Conference Location

  • United States