Document Detail


Targeted p21WAF1/CIP1 activation by RNAa inhibits hepatocellular carcinoma cells.
MedLine Citation:
PMID:  22909100     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double-stranded RNA (dsRNA), also known as small activating RNA (saRNA). p21(WAF1/CIP1) (p21) is a putative tumor suppressor gene due to its role as a key negative regulator of the cell cycle and cell proliferation. It is frequently downregulated in cancer including hepatocellular carcinoma (HCC), but is rarely mutated or deleted, making it an ideal target for RNAa-based overexpression to restore its tumor suppressor function. In the present study, we investigated the antigrowth effects of p21 RNAa in HCC cells. Transfection of a p21 saRNA (dsP21-322) into HepG2 and Hep3B cells significantly induced the expression of p21 at both the mRNA and protein levels, and inhibited cell proliferation and survival. Further analysis of dsP21-322 transfected cells revealed that dsP21-322 arrested the cell cycle at the G(0)/G(1) phase in HepG2 cells but at G(2)/M phase in Hep3B cells which lack functional p53 and Rb genes, and induced both early and late stage apoptosis by activating caspase 3 in both cell lines. These results demonstrated that RNAa of p21 has in vitro antigrowth effects on HCC cells via impeding cell cycle progression and inducing apoptotic cell death. This study suggests that targeted activation of p21 by RNAa may be explored as a novel therapy for the treatment of HCC.
Authors:
Mika Kosaka; Moo Rim Kang; Glen Yang; Long-Cheng Li
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-08-21
Journal Detail:
Title:  Nucleic acid therapeutics     Volume:  22     ISSN:  2159-3345     ISO Abbreviation:  Nucleic Acid Ther     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-03     Completed Date:  2013-02-28     Revised Date:  2013-10-10    
Medline Journal Info:
Nlm Unique ID:  101562758     Medline TA:  Nucleic Acid Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  335-43     Citation Subset:  IM    
Affiliation:
Department of Urology and Helen-Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Carcinoma, Hepatocellular
Caspase 3 / metabolism
Cell Cycle Checkpoints / genetics
Cell Proliferation
Cell Survival / genetics
Cyclin-Dependent Kinase Inhibitor p21 / genetics*,  metabolism
Hep G2 Cells
Humans
RNA, Double-Stranded / genetics*
Transcriptional Activation*
Grant Support
ID/Acronym/Agency:
1R01GM090293-0109/GM/NIGMS NIH HHS; 1R21CA131774/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/RNA, Double-Stranded; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3
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