MicroRNA let-7a regulates angiogenesis by targeting TGFBR3 mRNA

J Cell Mol Med. 2019 Jan;23(1):556-567. doi: 10.1111/jcmm.13960. Epub 2018 Nov 22.

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.

Keywords: Let-7a; TGFBR3; TGFβ signalling; angiogenesis; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Proteoglycans / genetics*
  • RNA Processing, Post-Transcriptional / genetics
  • RNA, Messenger / genetics*
  • Receptors, Transforming Growth Factor beta / genetics*

Substances

  • MicroRNAs
  • Proteoglycans
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • betaglycan