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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-miRNAmiR-596directly targetingLGALS3BP/Mac-2 BP/90K. DNA hypermethylation of CpG island located 5′-upstream ofmiR-596gene 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, respectively) in a tumor-specific manner. The ectopic transfection of double-stranded RNA (dsRNA) mimickingmiR-596or specific small interfering RNA forLGALS3BPsignificantly induced growth inhibition and apoptosis in cell lines lackingmiR-596expression or overexpressingLGALS3BP, respectively, in a manner associated with a suppression of ERK1/2 phosphorylation. Moreover, we also mention the effect of dsRNA mimickingmiR-596on the growth of an OSCC cell linein vivo. Our findings define a central role formiR-596in OSCC and suggest the potential ofmiR-596as an anticancer agent for miRNA replacement therapy in OSCC.

carcinogenesis

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