Abstract 1846: Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer.

Abstract

The incidence and mortality statistics for oral squamous cell carcinoma (OSCC) were 10th and 12th, respectively, in human cancers diagnosed worldwide in 2008. In this study, to identify novel tumor-suppressive microRNAs (TS-miRNAs) and their direct targets in OSCC, we performed methylation-based screening for 43 miRNAs encoded by 46 miRNA genes located within 500bp downstream of 40 CpG islands and genome-wide gene expression profiling in combination with a prediction database analysis, respectively, in 18 cell lines, resulting in the identification of a novel TS-miRNA miR-596 directly targeting LGALS3BP/Mac-2 BP/90K. DNA hypermethylation of CpG island located 5’-upstream of miR-596 gene was frequently observed in OSCC cell lines (100% of 18 cell lines) and primary OSCC cases (46.2% and 76.3% of 26 Japanese and 38 Thais primary cases) in a tumor-specific manner. The ectopic transfection of double-stranded RNA (dsRNA) mimicking miR-596 or specific siRNA for LGALS3BP significantly induced growth inhibition and apoptosis in cell lines lacking miR-596 expression or overexpressing LGALS3BP, respectively, in a manner associated with a suppression of ERK1/2 phosphorylation. Moreover, we also mention the effect of dsRNA mimicking miR-596 on the growth of an OSCC cell line in vivo. Our findings define a central role for miR-596 in OSCC and suggest the potential of miR-596 as an anti-cancer agent for miRNA replacement therapy in OSCC. Citation Format: Ken-ichi Kozaki, Hironori Endo, Tomoki Muramatsu, Mayuko Furuta, Narikazu Uzawa, Atiphan Pimkhaokham, Teruo Amagasa, Johji Inazawa. Potential of tumor-suppressive miR-596 targeting LGALS3BP as a therapeutic agent in oral cancer. [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 1846. doi:10.1158/1538-7445.AM2013-1846