title: SirT1 knockdown potentiates radiation-induced bystander effect through promoting c-Myc activity and thus facilitating ROS accumulation.
abstract: Radiation-induced bystander effect (RIBE) has important implications for secondary cancer risk assessment during cancer radiotherapy, but the bystander signaling processes, especially under hypoxic condition, are still largely unclear. The present study found that micronuclei (MN) formation could be induced in the non-irradiated HL-7702 hepatocyte cells after being treated with the conditioned medium from irradiated hepatoma HepG2 and SK-Hep-1 cells under either normoxia or hypoxia. This bystander response was dramatically diminished or enhanced when the SirT1 gene of irradiated hepatoma cells was overexpressed or knocked down, respectively, especially under hypoxia. Meanwhile, SirT1 knockdown promoted transcriptional activity for c-Myc and facilitated ROS accumulation. But both of the increased bystander responses and ROS generation due to SirT1-knockdown were almost completely suppressed by c-Myc interference. Moreover, ROS scavenger effectively abolished the RIBE triggered by irradiated hepatoma cells even with SirT1 depletion. These findings provide new insights that SirT1 has a profound role in regulating RIBE where a c-Myc-dependent release of ROS may be involved.
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China; Central Laboratory, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Yuexia
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Tu
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Mingyuan
authors.initials: M
authors.lastname: He
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ye
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Institute of Radiation Medicine, Fudan University, Shanghai, China. Electronic address: clshao@shmu.edu.cn.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Shao
mesh_terms: D024201:Bystander Effect / Q000235:genetics / Q000528:radiation effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D015687:Cell Hypoxia / Q000235:genetics / Q000528:radiation effects; D005720:Gamma Rays; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Hepatoma and hepatocyte cells; Oxygen conditions; RIBE; ROS; SirT1 and c-Myc