title: Systematic analysis of time-series gene expression data on tumor cell-selective apoptotic responses to HDAC inhibitors.
abstract: SAHA (suberoylanilide hydroxamic acid or vorinostat) is the first nonselective histone deacetylase (HDAC) inhibitor approved by the US Food and Drug Administration (FDA). SAHA affects histone acetylation in chromatin and a variety of nonhistone substrates, thus influencing many cellular processes. In particularly, SAHA induces selective apoptosis of tumor cells, although the mechanism is not well understood. A series of microarray experiments was recently conducted to investigate tumor cell-selective proapoptotic transcriptional responses induced by SAHA. Based on that gene expression time series, we propose a novel framework for detailed analysis of the mechanism of tumor cell apoptosis selectively induced by SAHA. Our analyses indicated that SAHA selectively disrupted the DNA damage response, cell cycle, p53 expression, and mitochondrial integrity of tumor samples to induce selective tumor cell apoptosis. Our results suggest a possible regulation network. Our research extends the existing research.
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Yun-feng
authors.initials: YF
authors.lastname: Qi
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Yan-xin
authors.initials: YX
authors.lastname: Huang
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China ; School of Computer Science and Information Technology, Northeast Normal University, Changchun 130117, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Li-hua
authors.initials: LH
authors.lastname: Zheng
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Yong-li
authors.initials: YL
authors.lastname: Bao
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Lu-guo
authors.initials: LG
authors.lastname: Sun
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, China.
authors.forename: Chun-lei
authors.initials: CL
authors.lastname: Yu
authors.affiliation: Department of General Internal Medicine, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Jiang
authors.affiliation: Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Northeast Normal University, Changchun 130024, China.
authors.forename: Yu-xin
authors.initials: YX
authors.lastname: Li
mesh_terms: D000465:Algorithms; D017209:Apoptosis; D002453:Cell Cycle; D016000:Cluster Analysis; D004249:DNA Damage; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D012984:Software; D013997:Time Factors; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat