Journal article
MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes
The Journal of clinical investigation, Vol.124(10), pp.4305-4319
10/01/2014
DOI: 10.1172/JCI77116
PMID: 25180607
Abstract
Metastasis causes most cancer deaths, but is incompletely understood. MicroRNAs can regulate metastasis, but it is not known whether a single miRNA can regulate metastasis in primary cancer models in vivo. We compared the expression of miRNAs in metastatic and nonmetastatic primary mouse sarcomas and found that microRNA-182 (miR-182) was markedly overexpressed in some tumors that metastasized to the lungs. By utilizing genetically engineered mice with either deletion of or overexpression of miR-182 in primary sarcomas, we discovered that deletion of miR-182 substantially decreased, while overexpression of miR-182 considerably increased, the rate of lung metastasis after amputation of the tumor-bearing limb. Additionally, deletion of miR-182 decreased circulating tumor cells (CTCs), while overexpression of miR-182 increased CTCs, suggesting that miR-182 regulates intravasation of cancer cells into the circulation. We identified 4 miR-182 targets that inhibit either the migration of tumor cells or the degradation of the extracellular matrix. Notably, restoration of any of these targets in isolation did not alter the metastatic potential of sarcoma cells injected orthotopically, but the simultaneous restoration of all 4 targets together substantially decreased the number of metastases. These results demonstrate that a single miRNA can regulate metastasis of primary tumors in vivo by coordinated regulation of multiple genes.
Details
- Title: Subtitle
- MicroRNA-182 drives metastasis of primary sarcomas by targeting multiple genes
- Creators
- Mohit Sachdeva - Department of Radiation OncologyJeffrey K Mito - Department of Radiation OncologyChang-Lung Lee - Department of Radiation OncologyMinsi Zhang - Department of Radiation OncologyZhizhong Li - Department of Radiation OncologyRebecca D Dodd - Department of Radiation OncologyDavid Cason - Department of Radiation OncologyLixia Luo - Department of Radiation OncologyYan Ma - Department of Radiation OncologyDavid Van Mater - Department of Radiation OncologyRebecca Gladdy - Department of Radiation OncologyDina C Lev - Department of Radiation OncologyDiana M Cardona - Department of Radiation OncologyDavid G Kirsch - Department of Radiation Oncology
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.124(10), pp.4305-4319
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI77116
- PMID
- 25180607
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 10/01/2014
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094730602771
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