1 220

Cited 40 times in

Antitumor Effects in Hepatocarcinoma of Isoform-Selective Inhibition of HDAC2.

Authors
 Yun-Han Lee  ;  Daekwan Seo  ;  Kyung-Ju Choi  ;  Jesper B. Andersen  ;  Min-Ah Won  ;  Mitsuteru Kitade  ;  Luis E. Gómez-Quiroz  ;  Adam D. Judge  ;  Jens U. Marquardt  ;  Chiara Raggi  ;  Elizabeth A. Conner  ;  Ian MacLachlan  ;  Valentina M. Factor  ;  Snorri S. Thorgeirsson 
Citation
 Cancer Research, Vol.74(17) : 4752-4761, 2014 
Journal Title
 Cancer Research 
ISSN
 0008-5472 
Issue Date
2014
Abstract
Histone deacetylase 2 (HDAC2) is a chromatin modifier involved in epigenetic regulation of cell cycle, apoptosis, and differentiation that is upregulated commonly in human hepatocellular carcinoma (HCC). In this study, we show that specific targeting of this HDAC isoform is sufficient to inhibit HCC progression. siRNA-mediated silencing of HDAC inhibited HCC cell growth by blocking cell-cycle progression and inducing apoptosis. These effects were associated with deregulation of HDAC-regulated genes that control cell cycle, apoptosis, and lipid metabolism, specifically, by upregulation of p27 and acetylated p53 and by downregulation of CDK6 and BCL2. We found that HDAC2 silencing in HCC cells also strongly inhibited PPARγ signaling and other regulators of glycolysis (ChREBPα and GLUT4) and lipogenesis (SREBP1C and FAS), eliciting a marked decrease in fat accumulation. Notably, systemic delivery of HDAC2 siRNA encapsulated in lipid nanoparticles was sufficient to blunt the growth of human HCC in a murine xenograft model. Our findings offer preclinical proof-of-concept for HDAC2 blockade as a systemic therapy for liver cancer.
Full Text
http://cancerres.aacrjournals.org/content/74/17/4752.long
DOI
10.1158/0008-5472.CAN-13-3531
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Won, Min Ah(원민아)
Lee, Yun Han(이윤한)
Choi, Kyung Ju(최경주)
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99749
사서에게 알리기
  feedback

qrcode

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

Browse