Myogenic transcription factors regulate pro-metastatic miR-182

Oncogene. 2016 Apr 7;35(14):1868-75. doi: 10.1038/onc.2015.252. Epub 2015 Aug 3.

Abstract

Approximately 30% of patients with soft-tissue sarcoma die from pulmonary metastases. The mechanisms that drive sarcoma metastasis are not well understood. Recently, we identified miR-182 as a driver of sarcoma metastasis in a primary mouse model of soft-tissue sarcoma. We also observed elevated miR-182 in a subset of primary human sarcomas that metastasized to the lungs. Here, we show that myogenic differentiation factors regulate miR-182 levels to contribute to metastasis in mouse models. We find that MyoD directly binds the miR-182 promoter to increase miR-182 expression. Furthermore, mechanistic studies revealed that Pax7 can promote sarcoma metastasis in vivo through MyoD-dependent regulation of pro-metastatic miR-182. Taken together, these results suggest that sarcoma metastasis can be partially controlled through Pax7/MyoD-dependent activation of miR-182 and provide insight into the role that myogenic transcription factors have in sarcoma progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Muscle Development / genetics
  • MyoD Protein / genetics*
  • MyoD Protein / metabolism
  • PAX7 Transcription Factor / genetics*
  • PAX7 Transcription Factor / metabolism
  • Promoter Regions, Genetic
  • Sarcoma / genetics*
  • Sarcoma / pathology

Substances

  • MicroRNAs
  • Mirn182 microRNA, human
  • MyoD Protein
  • PAX7 Transcription Factor
  • PAX7 protein, human