Inhibition of MiR-199a-5p reduced cell proliferation in autosomal dominant polycystic kidney disease through targeting CDKN1C

Med Sci Monit. 2015 Jan 15:21:195-200. doi: 10.12659/MSM.892141.

Abstract

Background: With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD) often causes renal failure, with many serious complications. However, there is no Food and Drug Administration (FDA) approved therapy available.

Material/methods: MiR-199a-5p level in ADPKD patient samples, rat model, and cell lines were determined with Realtime PCR assay. After miR-199a-5p inhibitor was transfected, we detected the cell proliferation and apoptosis using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally, TargetScan version 5.1 was used to predict the miRNA target and the target gene of miR-199a-5p was proved by a Luciferase assay.

Results: We identified a dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines. Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation and induced cell apoptosis. We found that miR-199a-5p might exert this effect through targeting CDKN1C/p57.

Conclusions: Up-regulation of miR-199a-5p in ADPKD tissues might promote cell proliferation through suppressing CDKN1C, suggesting miR-199a-5p as a novel target for ADPKD treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p57 / genetics
  • Cyclin-Dependent Kinase Inhibitor p57 / metabolism*
  • Disease Models, Animal
  • Heterozygote
  • Humans
  • Kidney / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Polycystic Kidney, Autosomal Dominant / genetics*
  • Polycystic Kidney, Autosomal Dominant / metabolism
  • Rats
  • Up-Regulation

Substances

  • CDKN1C protein, human
  • Cyclin-Dependent Kinase Inhibitor p57
  • MIRN199 microRNA, rat
  • MicroRNAs
  • mirn199 microRNA, human