title: Genetically engineered oncolytic adenovirus induces autophagic cell death through an E2F1-microRNA-7-epidermal growth factor receptor axis.
abstract: 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.
authors.affiliation: Center for Gene and Cell Therapy, Okayama University Hospital, Okayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tazawa
authors.forename: Shuya
authors.initials: S
authors.lastname: Yano
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Yoshida
authors.forename: Yasumoto
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Yuuri
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuroda
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ouchi
authors.forename: Teppei
authors.initials: T
authors.lastname: Onishi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Uno
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kagawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Urata
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D001343:Autophagy / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D003588:Cytopathogenic Effect, Viral; D050687:E2F1 Transcription Factor / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D005818:Genetic Engineering; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D050130:Oncolytic Virotherapy; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D050687:E2F1 Transcription Factor; D066246:ErbB Receptors; D035683:MicroRNAs; C493753:E2F1 protein, human; C549242:MIRN7-1 microRNA, human