Functional analysis of miR-199a-3p in tumor endothelial cells

Tumor endothelial cells (TECs) play a key role in tumor growth and metastasis. They exhibit distinct phenotypic and functional features compared with normal endothelial cells (NECs). Although microRNAs (miRNAs) play diverse roles in tumor progression, the differences in the miRNA expression profiles between TECs and NECs and their role in the TEC phenotype remain unclear.In this study, we isolated NECs and TECs from non-tumor and tumor regions of human renal cancer tissues and conducted an miRNA array analysis. Of the 13 differentially expressed miRNAs, miR-199a-3p was expressed the highest in TECs. Overexpression of miR-199a-3p in NECs significantly enhanced their proliferation, migration, and invasion.Target gene analysis using four databases identified CD151 as a potential target of miR-199a-3p. CD151 expression was downregulated in TECs compared with NECs, and miR-199a-3p transfection decreased CD151 expression in NECs. CD151 knockdown by siRNA promotes cell proliferation, migration, and invasion, and reduces cell adhesion to the extracellular matrix. Moreover, miR-199a-3p overexpression and CD151 silencing upregulated MMP2 expression in TECs. Taken together, these results suggest that miR-199a-3p contributes to the proangiogenic phenotype in TECs by suppressing CD151 expression.Key words: miR-199a-3p, tumor endothelial cells, CD151, angiogenesis, cell migration and invasion.