Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis
dc.contributor.author | Mitra, A.K. | |
dc.contributor.author | Chiang, C.Y. | |
dc.contributor.author | Tiwari, P. | |
dc.contributor.author | Tomar, S. | |
dc.contributor.author | Watters, K.M. | |
dc.contributor.author | Peter, M.E. | |
dc.contributor.author | Lengyel, E. | |
dc.contributor.department | Department of Medicine, IU School of Medicine | en_US |
dc.date.accessioned | 2017-07-12T18:56:04Z | |
dc.date.available | 2017-07-12T18:56:04Z | |
dc.date.issued | 2015-11-26 | |
dc.description.abstract | The cross-talk between ovarian cancer (OvCa) cells and the metastatic microenvironment is an essential determinant of successful colonization. MicroRNAs (miRNAs) have several critical roles during metastasis; however, the role of microenvironmental cues in the regulation of miRNAs in metastasizing cancer cells has not been studied. Using a three-dimensional culture model that mimics the human omentum, one of the principal sites of OvCa metastasis, we identified and characterized the microenvironment-induced downregulation of a tumor suppressor miRNA, miR-193b, in metastasizing OvCa cells. The direct interaction of the OvCa cells with mesothelial cells, which cover the surface of the omentum, caused a DNA methyltransferase 1-mediated decrease in the expression of miR-193b in the cancer cells. The reduction in miR-193b enabled the metastasizing cancer cells to invade and proliferate into human omental pieces ex vivo and into the omentum of a mouse xenograft model of OvCa metastasis. The functional effects of miR-193b were mediated, in large part, by the concomitant increased expression of its target, urokinase-type plasminogen activator, a known tumor-associated protease. These findings link paracrine signals from the microenvironment to the regulation of a key miRNA in cancer cells. Targeting miR-193b, which is essential for metastatic colonization of cancer cells could prove effective in the treatment of OvCa metastasis. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Mitra, A., Chiang, C., Tiwari, P., Tomar, S., Watters, K., Peter, M., & Lengyel, E. (2015). Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis. Oncogene, 34(48), 5923–5932. http://doi.org/10.1038/onc.2015.43 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/13410 | |
dc.language.iso | en_US | en_US |
dc.publisher | SpringerNature | en_US |
dc.relation.isversionof | 10.1038/onc.2015.43 | en_US |
dc.relation.journal | Oncogene | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | miR-193b | en_US |
dc.subject | Ovarian cancer | en_US |
dc.subject | Metastasis | en_US |
dc.subject | Mesothelial cells | en_US |
dc.subject | uPA | en_US |
dc.title | Microenvironment-induced downregulation of miR-193b drives ovarian cancer metastasis | en_US |
dc.type | Article | en_US |