Identification of microRNA-203 as a suppressor of invasion in cancer

Objectives: Recent cumulative evidences show that microRNAs (miRNAs) play important roles in the invasion and metastasis of various cancers. miRNA binds to the 3'-UTR of specific target mRNA and suppresses translation or induces degradation of the target mRNA. To identify miRNAs involved in EMT and invasion of oral cancer, we compared the gene expression profiles between MSCC-1 and MSCC-Inv1 cells. We previously established highly invasive clone, MSCC-inv1 cells from MSCC-1 cells by using in vitro invasion assay. MSCC-Inv1 cells possessed EMT features. Several miRNAs including miR-200 family and miR-203 were downregulated in MSCC-inv1 cells. In this study, we focused on miR-203 and investigated the role of miR-203 in EMT and invasion of oral cancer. Methods: Real time PCR was applied to compare the expression levels of miR-203 in several oral cacner cell lines and normal keratinocytes. Then, we performed the invasion assay in miR-203 transfected or miR-203 inhibitor transfected cells. Moreover, we examined the expression level of miR-203 in TGF-beta-induced EMT model. Results: Reduced expression of miR-203 was observed in oral cancer cells with EMT features, in comparison with oral cancer cells without EMT features. Overexpression of miR-203 suppressed the invasive ability of MSCC-inv1 cells without miR-203 expression, and inhibition of miR-203 promoted the invasion of HSC2 cells with miR-203 expression. Moreover, miR-203 expression was downregulated in Panc-1 cells (human pancreatic cancer cells) after TGF-beta treatment. Interestingly, transfection with miR-203 inhibited EMT induction by TGF-beta in Panc-1 cells. Conclusion: miR-203 may be involved in the invasion and EMT induction of oral cancer cells.