Myogenic transcription factors regulate pro-metastatic miR-182
| Autor: | Youngbaek Kim, Yan Ma, William C. Eward, Mohit Sachdeva, Jeffrey K. Mito, Leslie G. Dodd, Dina Lev, David G. Kirsch, Rebecca D. Dodd, Brian E. Brigman |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Cellular differentiation Biology MyoD Muscle Development Article Metastasis 03 medical and health sciences Mice MyoD Protein Cell Line Tumor microRNA Genetics medicine Animals Humans Promoter Regions Genetic Molecular Biology Transcription factor Regulation of gene expression PAX7 Transcription Factor Cell Differentiation Sarcoma medicine.disease 3. Good health Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Immunology Cancer research |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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