Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis

Int J Cancer. 2012 Dec 15;131(12):2939-50. doi: 10.1002/ijc.27589. Epub 2012 Apr 30.


Autophagy is known to have a cytoprotective role under various cellular stresses; however, it also results in robust cell death as an important safeguard mechanism that protects the organism against invading pathogens and unwanted cancer cells. Autophagy is regulated by cell signalling including microRNA (miRNA), a post-transcriptional regulator of gene expression. Here, we show that genetically engineered telomerase-specific oncolytic adenovirus induced miR-7 expression, which is significantly associated with its cytopathic activity in human cancer cells. Virus-mediated miR-7 upregulation depended on enhanced expression of the E2F1 protein. Ectopic expression of miR-7 suppressed cell viability and induced autophagy by inhibiting epidermal growth factor receptor (EGFR) expression. Our results suggest that oncolytic adenovirus induces autophagic cell death through an E2F1-miR-7-EGFR pathway in human cancer cells, providing a novel insight into the molecular mechanism of an anticancer virotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / physiology*
  • Autophagy / physiology*
  • Cell Death / physiology*
  • Cytopathogenic Effect, Viral
  • E2F1 Transcription Factor / physiology*
  • ErbB Receptors / metabolism*
  • Genetic Engineering*
  • Humans
  • MicroRNAs / physiology*
  • Oncolytic Virotherapy*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction


  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MIRN7 microRNA, human
  • MicroRNAs
  • ErbB Receptors