circ_0037128/miR-17-3p/AKT3 axis promotes the development of diabetic nephropathy

Gene. 2021 Jan 10:765:145076. doi: 10.1016/j.gene.2020.145076. Epub 2020 Aug 27.

Abstract

Circular RNAs (circRNAs) play vital roles in the development of diabetic nephropathy (DN). In this study, we investigated the function of circ_0037128 and molecular mechanism via which it regulates diabetic nephropathy development. It was found that expression of circ_0037128 was significantly increased in mouse DN model and high glucose treated mesangial cells (MCs), and circ_0037128 loss-of-function led to reduced cell proliferation and fibrosis in vitro. Moreover, miR-17-3p acts as competitive endogenous RNA (ceRNA) that directly interacts with circ_0037128 through its miRNA response elements (MREs). Consistently, expression of miR-17-3p was remarkably down-regulated in DN model, and negatively regulated cell proliferation and fibrosis. Further investigations revealed that AKT3 was the putative target of miR-17-3p, whose expression was elevated in DN model. In conclusion, we have characterized the function of a novel circ_0037128 and illustrated the significance of circ_0037128-miR-17-3p-AKT3 axis in DN pathogenesis.

Keywords: AKT3; Circ_0037128; Diabetic nephropathy; miR-17-3p.

MeSH terms

  • Animals
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell-Free Nucleic Acids / genetics*
  • Cell-Free Nucleic Acids / metabolism*
  • Diabetes Mellitus / genetics
  • Diabetic Nephropathies / genetics*
  • Disease Models, Animal
  • Fibrosis / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Mice
  • MicroRNAs / genetics

Substances

  • Cell-Free Nucleic Acids
  • MicroRNAs
  • Mirn17 microRNA, mouse