title: Myogenic transcription factors regulate pro-metastatic miR-182.
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.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Dodd
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sachdeva
authors.affiliation: Department Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Mito
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Eward
authors.affiliation: Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Brigman
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Pathology, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Dodd
authors.affiliation: Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.affiliation: The Sarcoma Research Center at The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Lev
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, NC, USA.|Department Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Kirsch
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D024510:Muscle Development / Q000235:genetics; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012509:Sarcoma / Q000235:genetics* / Q000473:pathology
chemical_list: D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D017570:MyoD Protein; D051763:PAX7 Transcription Factor; C497321:PAX7 protein, human