The human adrenocortical carcinoma SW13 cell line has two subtypes that are phenotypically distinct. The SW13- subtype is highly proliferative and epithelial-like, while the SW13+ subtype is slow growing, motile, and mesenchymal-like. These differences are mediated in part by the post-transcriptional regulation of BRM, which is expressed in SW13+ cells, and not detectable in SW13- cells. While treatment with histone deacetylase inhibitors (HDACi) can force cells to transition from SW13- to SW13+, the epigenetic mechanisms involved in the subtype switch are unknown. Recently, it was shown that miR-199a is a potent negative regulator of BRM expression in many epithelial tumor cell lines. Given this, we examined the expression of miR-199a in the two SW13 subtypes, and indeed found that miR-199a expression was significantly higher in the BRM-deficient SW13- cells than the BRM-expressing SW13+ cells. To begin to further assess the involvement of miR-199a in the SW13 subtype switch, SW13+ and SW13- cells were treated with either a miR-199a mimic or miR-199a inhibitor, respectively and assessed for differences in BRM mRNA and protein expression, as well changes in cell-type morphology. Our results indicate that although miR-199a can mediate differences in BRM expression, miR-199a alone is not sufficient to induce a full subtype conversion as evidenced by retention of subtype morphology following miR-199a inhibition and over-expression. We are currently investigating the role of miR-199a in HDACi mediated subtype conversion, as well as the expression of other miRNA and their targets that are differentially expressed between the two SW13 subtypes.
Citation Format: Tracy Gerona, McKale Davis, Elizabeth Hull. Contribution of miR-199a to subtype switching of the SW13 adrenocortical carcinoma cell line. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1116.