title: KAT5 silencing induces apoptosis of GBC-SD cells through p38MAPK-mediated upregulation of cleaved Casp9.
abstract: The poor overall prognosis of Gallbladder carcinoma (GBC) patients and the limited therapeutic regimens for these patients demonstrates the need for better therapeutic modalities, while the growing evidences have indicated that those genes contributed to epigenetic regulation may serve as therapeutic targets. The function of histone acetylation on growth and survival of GBC cells remains unknown. In present study, an RNAi screening of 16 genes involving histone acetyltransferases (HATs) was applied to GBC-SD cells and we found that KAT5 knockdown specifically inhibits the proliferation of GBC-SD cells by casp9-mediated apoptosis. Microarray data analysis showed that KAT5 RNAi may result in cleaved casp9 upregulation through p38MAPK activation in GBC-SD cells. The mRNA expression level of KAT5 was significantly upregulated in GBC tissues than in the adjacent normal tissues. In consistence with the mRNA level, the protein expression of KAT5 was markedly increased in tissues from patients with poor prognosis than those with good prognosis. These findings strongly indicated that KAT5 was implicated in GBC tumorigenesis and that its expression level was associated with the prognosis. Our work may also provide a potential therapeutic target for treatment of GBC patients.
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Fei-Ling
authors.initials: FL
authors.lastname: Feng
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Bai-He
authors.initials: BH
authors.lastname: Zhang
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Qing-Bao
authors.initials: QB
authors.lastname: Cheng
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Tan
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Xiang-Ji
authors.initials: XJ
authors.lastname: Luo
authors.affiliation: Department of Biliary I, Third Affiliated Hospital of PLA Second Military Medical University Shanghai, China.
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D053453:Caspase 9 / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D020868:Gene Silencing; D051548:Histone Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D000074443:Lysine Acetyltransferase 5; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D048051:p38 Mitogen-Activated Protein Kinases; D053453:Caspase 9
keywords: Gallbladder carcinoma; KAT5; RNAi screening; histone acetyltransferases; p38MAPK