RESUMO
Research has shown that some circular RNAs (circRNA) are abnormally expressed in the process of myocardial fibrosis, but the mechanism behind this was unknown. In the process of inducing cardiac fibroblast (CF) activation with TGF-ß1 or Ang II, the expression of circRNA circ_BMP2K and miR-455-3p were significantly inhibited, whereas the expression of SUMO1 was promoted. The results from our dual luciferase reporter gene assays, RIP assays, and pull-down assays show that miR-455-3p directly binds circ_BMP2K, thereby mutually promoting their expression levels. SUMO1 is a target gene of miR-455-3p, and circ_BMP2K enhances the inhibitory effects of miR-455-3p on the expression of SUMO1. Further study showed that both circ_BMP2K and miR-455-3p inhibited the expression of alpha-SMA as well as type I and type III collagen, whereas SUMO1 promoted their expression, and miR-455-3p inhibitors or overexpression of SUMO1 reversed the effects of circ_BMP2K and miR-455-3p. Circ_BMP2K and miR-455-3p inhibits cell proliferation and migration and promotes the apoptosis of CFs, but SUMO1 has the opposite effects; miR-455-3p inhibitors or overexpression of SUMO1 reverses the effects of circ_BMP2K and miR-455-3p. Thus, circ_BMP2K promotes the expression of miR-455-3p, down-regulates the expression of SUMO1, and finally, inhibits the activation, growth, and migration of CFs. These results could provide important therapeutic targets and a theoretical basis for regulating the process of myocardial fibrosis.
