Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/49396
Title: Genomic Analysis of Chemo-Resistance to HDAC inhibitor in Gastric Cancer cells
Authors: ZHU YANSONG
Keywords: genomics, chemo-resistance, RNH1, HDAC inhibitor,ROS, gastric cancer
Issue Date: 2-May-2013
Source: ZHU YANSONG (2013-05-02). Genomic Analysis of Chemo-Resistance to HDAC inhibitor in Gastric Cancer cells. ScholarBank@NUS Repository.
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
URI: http://scholarbank.nus.edu.sg/handle/10635/49396
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
ZhuYS.pdf3.84 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

110
checked on Dec 11, 2017

Download(s)

311
checked on Dec 11, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.