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RNH1 regulation of reactive oxygen species contributes to histone deacetylase inhibitor resistance in gastric cancer cells.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Zhu Y,Das K,Wu J,Lee MH,Tan P

doi

10.1038/onc.2013.104

subject

Has Abstract

pub_date

2014-03-20 00:00:00

pages

1527-37

issue

12

eissn

0950-9232

issn

1476-5594

pii

onc2013104

journal_volume

33

pub_type

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