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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.

SUBMITTER: Dodd RD

PROVIDER: S-EPMC4523886 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Myogenic transcription factors regulate pro-metastatic miR-182.

Dodd R D RD Sachdeva M M Mito J K JK Eward W C WC Brigman B E BE Ma Y Y Dodd L L Kim Y Y Lev D D Kirsch D G DG

Oncogene 20150803 14

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 f ...[more]

PMID: 26234681

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