Myogenic transcription factors regulate pro-metastatic miR-182.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Dodd, RD; Sachdeva, M; Mito, JK; Eward, WC; Brigman, BE; Ma, Y; Dodd, L; Kim, Y; Lev, D; Kirsch, DG

Published Date

  • April 7, 2016

Published In

Volume / Issue

  • 35 / 14

Start / End Page

  • 1868 - 1875

PubMed ID

  • 26234681

Pubmed Central ID

  • 26234681

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

Digital Object Identifier (DOI)

  • 10.1038/onc.2015.252

Language

  • eng

Conference Location

  • England