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Author (up) Zhu, Y.; Das, K.; Wu, J.; Lee, M.H.; Tan, P.
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  Title RNH1 regulation of reactive oxygen species contributes to histone deacetylase inhibitor resistance in gastric cancer cells Type Journal Article
  Year 2013 Publication Oncogene Abbreviated Journal Oncogene  
  Volume Issue Pages  
  Abstract Histone deacetylase inhibitors (HDACis) are a promising class of anticancer epigenetic drugs, however, molecular factors influencing the responses of individual tumors to HDACi therapies remain obscure. Here, we sought to identify genes associated with HDACi resistance in gastric cancer. Treating a panel of 17 gastric cancer cell lines with multiple HDACi compounds (trichostatin A, SAHA and MS275), we identified two distinct classes of lines exhibiting either HDACi sensitivity or resistance. Genomic comparisons between the sensitive and resistant classes using two independent microarray platforms identified RNH1, encoding a ribonuclease inhibitor, as a gene highly expressed in HDACi-resistant lines. Using genetic knockdown and overexpression assays, we show that RNH1 is both necessary and sufficient to induce HDACi resistance, and that RNH1 is likely to mediate this resistance through the dampening of HDACi-induced reactive oxygen species (ROS) in cancer cells. The discovery of RNH1 as a regulator of HDACi resistance in gastric cancer highlights a functional role for ROS induction in the cellular effects of this important drug class.Oncogene advance online publication, 15 April 2013; doi:10.1038/onc.2013.104.  
  Address 1] Cancer and Stem Cell and Biology, Duke-NUS Graduate Medical School, Singapore [2] Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0950-9232 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23584480 Approved no  
  Call Number @ @ Serial 39133  
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