MicroRNA-20a-5p Downregulation by Atorvastatin: A Potential Mechanism Involved in Lipid-Lowering Therapy

Int J Mol Sci. 2022 Apr 30;23(9):5022. doi: 10.3390/ijms23095022.

Abstract

The treatment of hypercholesterolemia is mainly based on statins. However, the response to pharmacological therapy shows high inter-individual variability, resulting in variable effects in both lipid lowering and risk reduction. Thus, a better understanding of the lipid-lowering mechanisms and response variability at the molecular level is required. Previously, we demonstrated a deregulation of the microRNA expression profile in HepG2 cells treated for 24 h with atorvastatin, using a microarray platform. In the present study, we evaluated the expression of hsa-miR-17-5p, hsa-miR-20a-5p and hsa-miR-106a-5p in hypercholesterolemic patients before and after atorvastatin treatment and in HepG2 cells treated for 24 h with atorvastatin The miRNA hsa-mir-20a-5p was repressed after atorvastatin treatment in hypercholesteremic subjects and in HepG2 cells in culture. Repression of hsa-mir-20a-5p increased LDLR gene and protein expression in HepG2 cells, while hsa-mir-20a-5p overexpression reduced LDLR gene and protein expression.

Keywords: atorvastatin; cardiovascular diseases; hypercholesterolemia; microRNA; statin.

MeSH terms

  • Atorvastatin* / pharmacology
  • Atorvastatin* / therapeutic use
  • Down-Regulation / genetics
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Hypercholesterolemia* / drug therapy
  • Hypercholesterolemia* / genetics
  • MicroRNAs* / drug effects
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • MIRN20a microRNA, human
  • MicroRNAs
  • Atorvastatin