title: SAHA regulates histone acetylation, Butyrylation, and protein expression in neuroblastoma.
abstract: Emerging evidence suggests that suberoylanilide hydroxamic acid (SAHA), a clinically approved HDAC inhibitor for cutaneous T-cell lymphoma, shows promising clinical benefits in neuroblastoma, the most common extra cranial solid neoplasm with limited choice of therapeutic intervention. However, the molecular mechanism under which the compound exerts its antitumor effect remains elusive. Here we report a quantitative proteomics study that determines changes of protein expression, histone lysine acetylation, and butyrylation in response to SAHA treatment. We detected and quantified 28 histone lysine acetylation and 18 histone lysine butyrylation marks, most of which are dramatically induced by SAHA. Importantly, we identified 11 histone Kbu sites as novel histone marks in human cells. Furthermore, quantitative proteomic analysis identified 5426 proteins, among which 510 proteins were up-regulated and 508 proteins were down-regulated (significant p value <0.05). The subsequent bioinformatics analysis identified distinct SAHA-response gene ontology (GO) categories and signaling pathways, including cellular metabolism and DNA-dependent pathways. Our study therefore reveals new histone epigenetic marks and offers key insights into the molecular mechanism by which SAHA regulates proteomic changes in neuroblastoma cells and identifies biomarker candidates for SAHA.
authors.affiliation: Pediatric Surgery Department, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine , 1650 Kongjiang Road, Shanghai 200092, P. R. China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Xu
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Zhixiang
authors.initials: Z
authors.lastname: Wu
authors.forename: Lili
authors.initials: L
authors.lastname: Qian
authors.forename: Lunzhi
authors.initials: L
authors.lastname: Dai
authors.forename: Xuelian
authors.initials: X
authors.lastname: Wan
authors.forename: Minjia
authors.initials: M
authors.lastname: Tan
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yeming
authors.initials: Y
authors.lastname: Wu
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D020148:Butyric Acid / Q000378:metabolism*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D053719:Tandem Mass Spectrometry; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D006877:Hydroxamic Acids; D009363:Neoplasm Proteins; D020148:Butyric Acid; D000077337:Vorinostat
keywords: histone deacetylase (HDAC); lysine acetylation; lysine butyrylation; neuroblastoma; quantitative proteomics; suberoylanilide hydroxamic acid (SAHA)