miR-21 regulates growth and EMT in lung cancer cells via PTEN/Akt/GSK3β signaling

Front Biosci (Landmark Ed). 2019 Jun 1;24:1426-1439.


miRNA-21 (miR-21) is overexpressed in various human cancers. Here, we show that miR-21 is overexpressed in human Non-Small Cell Lung Cancer (NSCLC) and that its up or down-regulation, respectively, increases or decreases cyclin D1 and cyclin E1 expression and coordinately promotes or inhibits proliferation of cancer cells. The perturbations of miR-21 also dramatically reduces or increases epithelial to mesenschymal transition (EMT). We show that regulation of proliferation and EMT are directed by PTEN/Akt/GSK3 beta signaling axis by regulating the expression of invasion markers including E-cadherin, vimentin, snail, slug and beta-catenin. Together, these findings show that miR-21 is a potential target for the development of treatment for NSCLC forms of human lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cyclins / genetics
  • Cyclins / metabolism
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Glycogen Synthase Kinase 3 beta / genetics
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / genetics*


  • Biomarkers, Tumor
  • Cyclins
  • MIRN21 microRNA, human
  • MicroRNAs
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human