HDAC1 Inactivation Induces Mitotic Defect and Caspase-IndependentAutophagic Cell Death in Liver Cancer

Collection with item attached
2012
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/479752.do
DOI
10.1371/journal.pone.0034265
Title
HDAC1 Inactivation Induces Mitotic Defect and Caspase-IndependentAutophagic Cell Death in Liver Cancer
Description
This work was supported by the Korean Ministry of the Environment via"The Eco-technopia 21 project" and by Public Welfare & Safety program,through the National Research Foundation of Korea (NRF), funded by theMinistry of Education, Science and Technology (2010-0020764); and by theNational Research Foundation of Korea (NRF) grant, funded by the Koreagovernment (MEST) (Grant No. 2011-0010705). The funders had no role instudy design, data collection and analysis, decision to publish, orpreparation of the manuscript.
abstract
Histone deacetylases (HDACs) are known to play a central role in the regulation of several cellular properties interlinked with the development and progression of cancer. Recently, HDAC1 has been reported to be overexpressed in hepatocellular carcinoma (HCC), but its biological roles in hepatocarcinogenesis remain to be elucidated. In this study, we demonstrated overexpression of HDAC1 in a subset of human HCCs and liver cancer cell lines. HDAC1 inactivation resulted in regression of tumor cell growth and activation of caspase-independent autophagic cell death, via LC3B-II activation pathway in Hep3B cells. In cell cycle regulation, HDAC1 inactivation selectively induced both p21(WAF1/Cip1) and p27(Kip1) expressions, and simultaneously suppressed the expression of cyclin D1 and CDK2. Consequently, HDAC1 inactivation led to the hypophosphorylation of pRb in G1/S transition, and thereby inactivated E2F/DP1 transcription activity. In addition, we demonstrated that HDAC1 suppresses p21(WAF1/Cip1) transcriptional activity through Sp1-binding sites in the p21(WAF1/Cip1) promoter. Furthermore, sustained suppression of HDAC1 attenuated in vitro colony formation and in vivo tumor growth in a mouse xenograft model. Taken together, we suggest the aberrant regulation of HDAC1 in HCC and its epigenetic regulation of gene transcription of autophagy and cell cycle components. Overexpression of HDAC1 may play a pivotal role through the systemic regulation of mitotic effectors in the development of HCC, providing a particularly relevant potential target in cancer therapy.
provenance
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language
English
author
Xie, Hong Jian
Noh, Ji Heon
Kim, Jeong Kyu
Jung, Kwang Hwa
Eun, Jung Woo
Bae, Hyun Jin
Kim, Min Gyu
Chang, Young Gyoon
Lee, Jung Young
Park, Hanna
Nam, Suk Woo
accessioned
2018-09-28T13:07:49Z
available
2018-09-28T13:07:49Z
issued
2012
citation
PLOS ONE(7): 4
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/479752.do
Funder
교육과학기술부
Funding Program
2단계연구중심대학육성(0.5)
Project ID
1345196466
Jurisdiction
Rep.of Korea
Project Name
BK Project Team for Biomedicalscience
rights
openAccess
type
article


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