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

Myogenic transcription factors regulate pro-metastatic miR-182.

Author information

1
Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
2
Department Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
3
Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
4
Department of Pathology, University of North Carolina, Chapel Hill, NC, USA.
5
Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
6
The Sarcoma Research Center at The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.

PMID:
26234681
PMCID:
PMC4523886
DOI:
10.1038/onc.2015.252
[Indexed for MEDLINE]
Free PMC Article

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