Abstract 4203: Overexpression of miR-26a-2 in human liposarcoma is correlated with poor patient survival

Approximately 90% of well-differentiated/de-differentiated LPS (WDLPS/DDLPS), the most common LPS subtype, have chromosomal amplification at 12q13-q15. Many protein-coding genes in the region, such as MDM2 and CDK4, have been studied as potential therapeutic targets for LPS treatment with minimal success. Within this amplicon near the MDM2 gene, our SNP array analysis identified frequent amplification of miR-26a-2. Besides being in the amplicon, we found that miR-26a-2 is overexpressed significantly in WDLPS/DDLPS, as well as in myxoid/round cell LPS (MRC). Furthermore, Kaplan-Meier survival analysis showed that overexpression of miR-26a-2 significantly correlated with poor patient survival in both types of LPS. Based on these findings, we hypothesized that miR-26a-2 plays an important role in LPS tumorigenesis, regardless of LPS subtypes. Overexpression of miR-26a-2 in LPS cells could help the growth and survival of cancer cells in a cell type-specific manner, including faster cell proliferation, faster cell migration, enhanced clonogenicity, suppressed adipocyte differentiation, and/or resistance to apoptosis. Inhibition of miR-26a-2 in LPS cells using anti-miR-26a-2 resulted in the opposite responses. To explain further the effect of miR-26a-2 overexpression in LPS cells, we performed in sillico analysis and identified 93 candidate targets of miR-26a-2. Among these candidate genes, we found that RCBTB1 (RCC1 and BTB domain containing protein 1) was located at 13q12.3-q14.3, a recurrent region of loss of heterozygosity (LOH) in human LPS. Indeed, overexpression of RCBTB1 made cells more susceptible to apoptosis. Likewise, inhibition of RCBTB1 made cells more resistant to apoptosis. In conclusion, our study reveals, for the first time, the contribution that miR-26a-2 makes to LPS tumorigenesis, partly through inhibiting RCBTB1. Our study shows that miR-26a-2 is a novel therapeutic target for human LPS. Citation Format: Dhong Hyun Tony Lee, Soroosh Amanat, Catherine Goff, Lawrence Weiss, Suzanne Cutter, Jonathan Said, Ngan Doan, Seishi Ogawa, Aiko Matsubara, Charles Forscher, H.Phillip Koeffler. Overexpression of miR-26a-2 in human liposarcoma is correlated with poor patient survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4203. doi:10.1158/1538-7445.AM2013-4203