LNCRNA CDKN2B-AS1 regulates mesangial cell proliferation and extracellular matrix accumulation via miR-424-5p/HMGA2

Yang Li1, Lin-Lin Zheng2, Deng-Gao Huang2

  • 1Department of Nephropathy, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan, China.

Abstract

Insights

Long noncoding RNA CDKN2B-AS1 promotes diabetic nephropathy by increasing cell proliferation and extracellular matrix accumulation. Silencing CDKN2B-AS1 may offer a therapeutic strategy for diabetic nephropathy treatment.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Genetics

Background:

  • Diabetic nephropathy (DN) is a complication of diabetes with abnormal expression of long noncoding RNA CDKN2B-AS1.
  • The precise mechanism of CDKN2B-AS1 in DN progression requires further investigation.

Purpose of the Study:

  • To elucidate the role of CDKN2B-AS1 in diabetic nephropathy.
  • To investigate the molecular mechanism involving microRNA-424-5p and HMGA2.

Main Methods:

  • Quantitative real-time PCR and western blot were used to detect expression levels of CDKN2B-AS1, miR-424-5p, and HMGA2.
  • Dual-luciferase reporter and RNA immunoprecipitation assays confirmed target associations.
  • Cell proliferation, ECM accumulation, and PI3K/AKT signaling were assessed in high glucose-treated human glomerular mesangial cells (HGMC).

Main Results:

  • CDKN2B-AS1 was upregulated, while miR-424-5p was downregulated in DN patients and HGMC cells exposed to high glucose.
  • CDKN2B-AS1 acted as a sponge for miR-424-5p, and HMGA2 was a target of miR-424-5p.
  • Silencing CDKN2B-AS1 or overexpressing miR-424-5p repressed cell proliferation, ECM accumulation, and the PI3K/AKT pathway, partly by targeting HMGA2.

Conclusions:

  • Knockdown of CDKN2B-AS1 inhibits HGMC proliferation, ECM accumulation, and PI3K/AKT signaling.
  • This effect is mediated by the upregulation of miR-424-5p and downregulation of HMGA2.
  • CDKN2B-AS1 plays a crucial role in DN pathogenesis via the miR-424-5p/HMGA2 axis.

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