title: Involvement of DDX6 gene in radio- and chemoresistance in glioblastoma.
abstract: CCRT (concomitant chemotherapy and radiation therapy) is often used for glioblastoma multiforme (GBM) treatment after surgical therapy, however, patients treated with CCRT undergo poor prognosis due to development of treatment resistant recurrence. Many studies have been performed to overcome these problems and to discover genes influencing treatment resistance. To discover potential genes inducing CCRT resistance in GBM, we used whole genome screening by infecting shRNA pool in patient-derived cell. The cells infected ~8,000 shRNAs were implanted in mouse brain and treated RT/TMZ as in CCRT treated patients. We found DDX6 as the candidate gene for treatment resistance after screening and establishing DDX6 knock down cells for functional validation. Using these cells, we confirmed tumor associated ability of DDX6 in vitro and in vivo. Although proliferation improvement was not found, decreased DDX6 influenced upregulated clonogenic ability and resistant response against radiation treatment in vivo and in vitro. Taken together, we suggest that DDX6 discovered by using whole genome screening was responsible for radio- and chemoresistance in GBM.
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Wonyoung
authors.initials: W
authors.lastname: Kang
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University of Medicine, Suwon, Seoul, Republic of Korea.
authors.forename: Sung Heon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Sa
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Paddison
authors.affiliation: Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Misuk
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Sungkyunkwan University of Medicine, Suwon, Seoul, Republic of Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.affiliation: Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Hwang
authors.affiliation: Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D049109:Cell Proliferation; D002470:Cell Survival; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D015723:Gene Library; D016678:Genome; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism; D000077204:Temozolomide; D015854:Up-Regulation
chemical_list: D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D003606:Dacarbazine; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases; D000077204:Temozolomide