miR-363 induces transdifferentiation of human kidney tubular cells to mesenchymal phenotype

Clin Exp Nephrol. 2016 Jun;20(3):394-401. doi: 10.1007/s10157-015-1167-2. Epub 2015 Sep 15.

Abstract

Background: microRNAs (miRNAs) are non-coding small RNAs that regulate embryonic development, cell differentiation and pathological processes via interaction with mRNA. Epithelial-mesenchymal transition (EMT) is pathological process that involves in a variety of diseases such as cancer or fibrosis.

Methods: In this study, we identified miR-363 as a potent inducer of EMT by microarray analysis in human kidney tubular cells, and analyzed the function and mechanisms of miR-363.

Results: Overexpression of miR-363 induced mesenchymal phenotypes with loss of epithelial phenotypes in human kidney tubular cells. In addition, in vitro scratch assay demonstrated that miR-363 promotes cell migration of primary culture of human kidney tubular cells. We identified TWIST/canonical WNT pathway as the downstream effecter of miR-363, and inhibition of canonical WNT by small molecule, IWR-1, attenuated EMT induced by miR-363.

Conclusion: miR-363 induces transdifferentiation of human kidney tubular cells via upregulation of TWIST/canonical WNT pathway.

Keywords: Cancer; EMT; Fibrosis; Kidney; miR-363; miRNA.

MeSH terms

  • Cell Line
  • Cell Movement
  • Cell Transdifferentiation* / drug effects
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Epithelial-Mesenchymal Transition* / drug effects
  • Gene Expression Profiling / methods
  • Humans
  • Imides / pharmacology
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism*
  • Kidney Tubules / pathology
  • MicroRNAs / drug effects
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Primary Cell Culture
  • Quinolines / pharmacology
  • RNA Interference
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Transfection
  • Transforming Growth Factor beta / pharmacology
  • Twist-Related Protein 1 / metabolism
  • Wnt Signaling Pathway

Substances

  • IWR-1 compound
  • Imides
  • MIRN363 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Quinolines
  • TWIST1 protein, human
  • Transforming Growth Factor beta
  • Twist-Related Protein 1
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases