title: Gene therapy for colorectal cancer by adenovirus-mediated siRNA targeting CD147 based on loss of the IGF2 imprinting system.
abstract: Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality phenomenon in CRC. Recently observed association of CRC with cluster of differentiation 147 (CD147) could provide a novel approach for gene therapy. In the present study, we investigated the feasibility of using adenovirus‑mediated siRNA targeting CD147 based on the IGF2 LOI system for targeted gene therapy of CRC. A novel adenovirus-mediated siRNA targeting CD147, rAd-H19-CD147mirsh, which was driven by the IGF2 imprinting system, was constructed. The results showed that the EGFP expression was detected only in the IGF2 LOI cell lines (HT-29 and HCT-8), but that no EGFP was produced in cell lines with maintenance of imprinting (MOI) (HCT116). Moreover, rAd-H19-CD147mirsh significantly inhibited the expression of CD147, decreased cell viability and invasive ability, and increased sensitivity to chemotherapeutic drugs only in the LOI cell lines in vitro. Furthermore, mice bearing HT-29 xenografted tumors, which received intratumoral administration of the rAd-H19-CD147mirsh, showed significantly reduced tumor growth and enhanced survival. We conclude that recombinant adenovirus-mediated siRNA targeting CD147 based on the IGF2 LOI system inhibited the growth of the LOI cells in vitro and in vivo, which would provide a novel approach for targeted CRC gene therapy.
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Bangshun
authors.initials: B
authors.lastname: He
authors.affiliation: College of Life Sciences, Nanjing Normal University, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Sun
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Qiwen
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Medical College, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Houqun
authors.initials: H
authors.lastname: Ying
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Kang
authors.initials: K
authors.lastname: Lin
authors.affiliation: Medical College, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Hongxin
authors.initials: H
authors.lastname: Peng
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, P.R. China.
authors.forename: Shukui
authors.initials: S
authors.lastname: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D051926:Basigin / Q000235:genetics* / Q000627:therapeutic use; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D019175:DNA Methylation / Q000235:genetics; D015316:Genetic Therapy; D018392:Genomic Imprinting; D019073:HT29 Cells; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000627:therapeutic use; D051379:Mice; D034741:RNA, Small Interfering / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: C497886:BSG protein, human; C035170:IGF2 protein, human; D034741:RNA, Small Interfering; D051926:Basigin; D007335:Insulin-Like Growth Factor II