title: RNAi screening identifies KAT8 as a key molecule important for cancer cell survival.
abstract: Histone acetyltransferases (HATs) regulate many critical cancer events, including transcriptional regulation of oncogene and tumor suppressors, chromatin structure and DNA damage response. Abnormal expression of HATs has been reported in a number of cancers. However, cellular functions of HATs in cancer and molecular mechanisms remain largely unclear. Here, we performed a lentiviral vector-mediated RNAi screen to systematically address the function of HATs in lung cancer cell growth and viability. We identified 8 HATs genes involved in A549 cell viability. Further experiments showed that KAT8 regulates G2/M cell cycle arrest through AKT/ERK-cyclin D1 signaling. Moreover, KAT8 inhibition led to p53 induction and subsequently reduced bcl-2 expression. Our results demonstrate an important role of KAT8 in cancer and suggest that KAT8 could be a novel cancer therapeutic target.
authors: Department of Pathophysiology, Norman Bathune College of Medical Sciences, Jilin University, Changchun, China.
authors: Shuang
authors: S
authors: Zhang
authors: Xianhong
authors: X
authors: Liu
authors: Yong
authors: Y
authors: Zhang
authors: Ying
authors: Y
authors: Cheng
authors: Yang
authors: Y
authors: Li
mesh_terms: D015153:Blotting, Western; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods*; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000502:physiology
chemical_list: D034741:RNA, Small Interfering; D051548:Histone Acetyltransferases; C496552:KAT8 protein, human
keywords: HATs; KAT8; RNAi screen; cell survival; cyclin D1; p53
references: Oncogene. 1996 Apr 4;12(7):1565-9
references: 8622873
references: Nat Rev Drug Discov. 2006 Sep;5(9):769-84
references: 16955068
references: J Mol Biol. 2001 Aug 17;311(3):433-44
references: 11492997
references: Mol Cell. 2006 Dec 28;24(6):807-8
references: 17189182
references: Hum Mol Genet. 2001 Feb 15;10(4):395-404
references: 11157802
references: Cancer Res. 2006 Jan 1;66(1):107-12
references: 16397222
references: Cell. 2000 Aug 18;102(4):463-73
references: 10966108
references: Blood. 1997 Oct 15;90(8):3130-5
references: 9376594
references: Nat Rev Drug Discov. 2007 Jul;6(7):556-68
references: 17599085
references: Cell. 2000 Sep 15;102(6):849-62
references: 11030628
references: EMBO J. 1999 Dec 1;18(23):6845-54
references: 10581258
references: Cancer Epidemiol Biomarkers Prev. 2009 Nov;18(11):3030-5
references: 19861517
references: Nat Rev Cancer. 2006 Jan;6(1):38-51
references: 16397526
references: Mol Cancer Ther. 2007 Sep;6(9):2391-8
references: 17876038
references: Brief Funct Genomics. 2013 May;12(3):231-43
references: 23325510
references: Nat Genet. 2000 Mar;24(3):300-3
references: 10700188
references: Int J Cancer. 2008 Mar 15;122(6):1207-13
references: 18058815
references: J Biol Chem. 1996 Aug 23;271(34):20608-16
references: 8702807
references: Cell. 1997 Feb 7;88(3):323-31
references: 9039259
references: Carcinogenesis. 2000 Aug;21(8):1537-46
references: 10910956
references: Anticancer Res. 2011 Dec;31(12):4115-25
references: 22199269
references: Mol Cell. 2006 Dec 28;24(6):827-39
references: 17189186
references: Annu Rev Biochem. 2001;70:81-120
references: 11395403
references: J Biol Chem. 2004 Dec 17;279(51):53015-22
references: 15471885
references: Mol Cell. 2006 Dec 28;24(6):841-51
references: 17189187
references: PLoS One. 2011;6(7):e22088
references: 21789216
references: Cell. 1995 Jan 27;80(2):293-9
references: 7834749
references: Nature. 2007 Aug 30;448(7157):1063-7
references: 17728759