Journal article
Myogenic transcription factors regulate pro-metastatic miR-182
Oncogene, Vol.35(14), pp.1868-1875
04/07/2016
DOI: 10.1038/onc.2015.252
PMCID: PMC4523886
PMID: 26234681
Abstract
Approximately thirty percent 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 play in sarcoma progression.
Details
- Title: Subtitle
- Myogenic transcription factors regulate pro-metastatic miR-182
- Creators
- Rebecca D Dodd - Department of Radiation Oncology, Duke University Medical Center, Durham, NCMohit Sachdeva - Department of Radiation Oncology, Duke University Medical Center, Durham, NCJeffrey K Mito - Department Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NCWilliam C Eward - Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NCBrian E Brigman - Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NCYan Ma - Department of Radiation Oncology, Duke University Medical Center, Durham, NCLeslie Dodd - Department of Pathology, University of North Carolina, Chapel Hill, North Carolina, 27599, USAYoungbaek Kim - Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South KoreaDina Lev - The Sarcoma Research Center at The University of Texas MD Anderson Cancer Center, Houston, Texas, USADavid G Kirsch - Department of Radiation Oncology, Duke University Medical Center, Durham, NC
- Resource Type
- Journal article
- Publication Details
- Oncogene, Vol.35(14), pp.1868-1875
- DOI
- 10.1038/onc.2015.252
- PMID
- 26234681
- PMCID
- PMC4523886
- ISSN
- 0950-9232
- eISSN
- 1476-5594
- Language
- English
- Date published
- 04/07/2016
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094567502771
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