title: SAHA treatment reveals the link between histone lysine acetylation and proteome in nonsmall cell lung cancer A549 Cells.
abstract: Suberoylanilide hydroxamic acid (SAHA) is a well-known pan HDAC inhibitor, and its clinical application (Vorinostat) has been demonstrated to treat nonsmall cell lung cancer (NSCLS). Nevertheless, the impact of SAHA treatment on histone lysine acetylation and proteome in NSCLS cells still need further elucidate. In NSCLS A549 cells, by using stable isotope labeling for cell culture (SILAC)-based quantitative proteomics, biochemistry assay, and bioinformatic analysis, here we for the first time comprehensively identified and quantified histone lysine acetylation in A549 cells toward SAHA treatment. Despite the fact that SAHA treatment significantly increased histone lysine acetylation in specific sites, unexpectedly, some important "histone markers" showed markedly decreased acetylation level. Further quantitative proteome studies showed that among totally quantifiable 2818 nonredundant proteins, 1355 proteins were with increased level and 1463 with decreased level in response to SAHA treatment. Bioinformatic analysis further revealed that those quantifiable proteins were mainly involved in multiple biological functions and metabolic and enzyme-regulated pathways as well as protein complexes. By establishing the link between histone modification and whole proteome in response to SAHA treatment in NSCLS cells, this study therefore may deepen our understanding of HDAC inhibitor-mediated cancer therapeutics.
authors.affiliation: Central Laboratory, Affiliated Provincial Hospital, Anhui Medical University, Hefei, China. powerwoo01@ahmu.edu.cn
authors.forename: Quan
authors.initials: Q
authors.lastname: Wu
authors.forename: Weiqing
authors.initials: W
authors.lastname: Xu
authors.forename: Lejie
authors.initials: L
authors.lastname: Cao
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Tieming
authors.initials: T
authors.lastname: He
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.forename: Wenting
authors.initials: W
authors.lastname: Li
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D002289:Carcinoma, Non-Small-Cell Lung; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D063990:Gene Ontology; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism; D058977:Molecular Sequence Annotation; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D020543:Proteome; D000077337:Vorinostat; D008239:Lysine