title: Cold-inducible RNA-binding protein, CIRP, inhibits DNA damage-induced apoptosis by regulating p53.
abstract: CIRP has been implicated in apoptosis, yet its mechanism of action remains unknown. To determine the role of CIRP in DNA damage-induced apoptosis, we performed CIRP overexpression and knockdown experiments to investigate the effects of CIRP on key molecules in apoptosis pathway. Etoposide treatment was used to induce DNA damage-induced apoptosis. We found that CIRP knockdown increased p53 level, which in turn up-regulated pro-apoptotic genes and down-regulated anti-apoptotic genes. In contrast, CIRP overexpression decreased p53 level, which in turn down-regulated pro-apoptotic genes and up-regulated anti-apoptotic genes. The change in the expression levels of pro-apoptotic and anti-apoptotic genes shifts the balance between life and death of cells. CIRP expression is upregulated by chronic inflammation, and this phenomenon provides an interesting interventional opportunity in cancers arising from chronic inflammation. Chronic inflammation up-regulates CIRP, which in turn inhibit apoptosis. Therefore, inhibiting the function of up-regulated CIRP may have a therapeutic value in cancer.
authors.affiliation: Department of Molecular Medicine, Graduate School of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea.
authors.forename: Hae Na
authors.initials: HN
authors.lastname: Lee
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; Department of Biomedical Informatics, Asan Medical Center, Seoul 138-736, Republic of Korea. Electronic address: smahn@amc.seoul.kr.
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Ahn
authors.affiliation: Department of Molecular Medicine, Graduate School of Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 406-840, Republic of Korea; Gachon Medical Research Institute, Gil Hospital, Incheon 405-760, Republic of Korea. Electronic address: hhjang@gachon.ac.kr.
authors.forename: Ho Hee
authors.initials: HH
authors.lastname: Jang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D053148:Caspase 3; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D005047:Etoposide / Q000494:pharmacology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C491073:BCL2L2 protein, human; C491390:CIRBP protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3
keywords: Anti-apoptotic genes; Apoptosis; CIRP; Etoposide; Pro-apoptotic genes; p53