title: DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells.
abstract: Pre-mRNA processing factor 19 (Prp19) activates pre-mRNA spliceosome and also mediates DNA damage response. Prp19 overexpression in cells with functional p53 leads to decreased apoptosis and increases cell survival after DNA damage. Here we showed that in hepatocellular carcinoma (HCC) cells with inactive p53 or functional p53, Prp19 was down-regulated due to the impaired stability under chemotherapeutic drug treatment. Silencing Prp19 expression enhanced apoptosis of HCC cells with or without chemotherapeutic drug treatment. Furthermore high level of Prp19 may inhibit chemotherapeutic drugs induced apoptosis in hepatocellular carcinoma cells through modulating myeloid leukemia cell differentiation 1 expression. These results indicated that targeting Prp19 may potentiate pro-apoptotic effect of chemotherapeutic agents on HCC.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Yi-An
authors.initials: YA
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.
authors.forename: Xi-Zhong
authors.initials: XZ
authors.lastname: Shen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D045643:DNA Repair Enzymes / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D004317:Doxorubicin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D055550:Protein Stability; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D000072260:RNA Splicing Factors; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C100852:MLF1 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D000072260:RNA Splicing Factors; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D003513:Cycloheximide; D045643:DNA Repair Enzymes; C417041:PRPF19 protein, human; D002945:Cisplatin