Aurora A, Aurora B and survivin are novel targets of transcriptional regulation by histone deacetylase inhibitors in non-small cell lung cancer

• DOI: 10.4161/cbt.7.9.6415
• Publication Date: 2010-12-28T17:00:57Z
• Authors: Xu-Hui Zhang; Mahadev Rao; Joseph A. Loprieato; Julie A. Hong; Ming Zhao; Guo-Zhu Chen; Ashley E. Humphries; Dao M. Nguyen; Jane B. Trepel; Xiaodan Yu; David S. Schrump
• Keywords: Aurora B kinase; Chromatin immunoprecipitation; Aurora kinase; Aurora inhibitor; Survivin; Aurora A kinase

Analysis of biopsies from a recent clinical trial suggested that Depsipeptide FK228 (DP) inhibits Aurora kinase expression in lung cancer cells. The present study was undertaken to confirm and extend these observations.Aurora A B mRNA levels cells were considerably higher than normal pulmonary epithelia. DP, TSA SAHA inhibited A, survivin with kinetics remarkably similar within individual cell lines, appeared coincide p53 status. These effects not observed following treatment geldanamycins. Inhibition transcription coincided decreased H3K9Ac H3K4Me2 activation marks, accumulation H3K9Me3, as well MBD1, MBD2 MBD3 repression marks the minimal promoter. Knockdown -2 or -3 did reproducibly abrogate inhibition by DP TSA. altered localization kinases survivin, resulting mitotic catastrophe cells.Aurora respiratory epithelia assessed using quantitative RT-PCR techniques. methods, Western blots used examine Auroras A/B, several related genes/proteins exposed TSA, Transient transfection promoter-reporter assays, chromatin immunoprecipitation (ChIP) techniques DP-mediated changes activity structure Confocal imaging on progression cells.Novel transcriptional regulatory mechanisms involving appear contribute cytotoxicity mediated HDAC inhibitors