MicroRNA let-7a regulates angiogenesis by targeting TGFBR3 mRNA

Abstract

Angiogenesis has a great impact on human health, owing to its participation in development, wound healing and the pathogenesis of several diseases. It has been reported that let-7a is a tumour suppressor, but whether it plays a role in angiogenesis is unclear. Here we showed that let-7a, a microRNA conserved in vertebrates, regulated angiogenesis by concomitantly down-regulating TGFBR3. Overexpression of let-7a or knockdown of TGFBR3 in cell culture inhibited the tube formation and reduced migration rate. Moreover, xenograft experiments showed that overexpression of let-7a or knockdown of TGFBR3 had smaller tumour size. Downstream genes, such as VEGFC and MMP9, were also down-regulated in let-7a overexpression or TGFBR3 knockdown groups. Therefore, our results revealed a novel mechanism that let-7a regulate angiogenesis through post-transcriptional regulation of TGFBR3.