Therapeutic microRNAs in polycystic kidney disease

Curr Opin Nephrol Hypertens. 2017 Jul;26(4):282-289. doi: 10.1097/MNH.0000000000000333.


Purpose of review: microRNAs (miRNAs) are short noncoding RNAs that function as sequence-specific inhibitors of gene expression. Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetic cause of end-stage kidney failure with limited treatment options. The realization that miRNA upregulation, and thus its gain-of-function, can drive the progression of ADPKD has raised the possibility that anti-miRs represent a novel drug class for this disorder.

Recent findings: A common set of miRNAs are aberrantly expressed in various murine models of polycystic kidney disease. In particular two miRNAs, miR-17 family and miR-21, are both upregulated in kidney cysts and promote ADPKD progression in mouse models. miR-17 rewires cyst epithelial metabolism to enhance cyst proliferation. On the other hand, miR-21 represses proapoptotic genes and thus inhibits cyst apoptosis. Importantly, an anti-miR-17 drug has advanced through preclinical ADPKD studies, whereas an anti-miR-21 drug has already cleared phase I clinical trial.

Summary: miRNAs have emerged as new regulators of ADPKD pathogenesis. Anti-miRs represent a feasible and an entirely new class of drugs for the treatment of ADPKD.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Regulation / genetics
  • Humans
  • Kidney Failure, Chronic / etiology
  • Mice
  • MicroRNAs / antagonists & inhibitors*
  • Oligonucleotides / therapeutic use*
  • Polycystic Kidney, Autosomal Dominant / complications
  • Polycystic Kidney, Autosomal Dominant / genetics
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Polycystic Kidney, Autosomal Dominant / therapy*
  • Up-Regulation


  • MIRN17 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs
  • Oligonucleotides