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Article: Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma
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TitlePrognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma
 
AuthorsLee, NP1
Tsang, FH1
Shek, FH1
Mao, M2 4
Dai, H2
Zhang, C2
Dong, S1
Guan, XY1
Poon, RTP1
Luk, JM1 3
 
KeywordseIF5A
Hepatocellular carcinoma
Hypusination
Oncofetal molecule
Targeted therapy
 
Issue Date2010
 
PublisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
 
CitationInternational Journal Of Cancer, 2010, v. 127 n. 4, p. 968-976 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.25100
 
AbstractUsing comparative proteomic and genomic approaches, the authors identified eukaryotic translation initiation factor 5A (eIF5A) as an oncofetal molecule highly abundant in mouse embryonic livers and human hepatocellular carcinoma (HCC) cell lines. To evaluate the oncogenic role and prognostic significance of eIF5A in HCC, we investigate the expression patterns of the two isoforms (eIF5A1 and eIF5A2) in a cohort of 258 HCC cases by cDNA microarray. Both eIF5A isoforms were expressed in the tumors, and clinically correlated eIF5A1 with more numbers of tumor nodules and eIF5A2 with tumor venous infiltration in HCC. In a separate cohort of 50 HCCs, high level of eIF5A2, but not eIF5A1, was associated with elevated levels of deoxyhypusine synthase and deoxyhypusine hydroxylase that catalyze post-translational hypusination of eIF5A protein. Interestingly, N1-guanyl-1,7-diaminoheptane (GC7), which is an inhibitor for the first step of eIF5A hypusination, was shown to significantly impair the cell proliferation and invasion of primary HCC cells (HepG2 and Hep3B). To further demonstrate the tumorigenic role associated with eIF5A, a drastic reduction of cell proliferation was associated with suppression of eIF5A2 by transfecting Hep3B, H2-P and H2-M HCC cells expressing high level of this isoform using small interfering RNA (siRNA) against eIF5A2. For these assays, a milder response was usually observed in normal hepatocyte cell line. Therefore, these findings suggest that eIF5A plays an important role in HCC tumorigenesis and metastasis, and targeting eIF5A hypusination by GC7 inhibitor or eIF5A2 by RNA interference (RNAi) may offer new therapeutic alternatives to HCC patients. © 2009 UICC.
 
ISSN0020-7136
2013 Impact Factor: 5.007
 
DOIhttp://dx.doi.org/10.1002/ijc.25100
 
ISI Accession Number IDWOS:000279971500024
Funding AgencyGrant Number
The University of Hong Kong
Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery
Funding Information:

Grant sponsor: This study was supported by a CRCG grant from The University of Hong Kong (to J.M.L.) and Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery (to R.T.P.)

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorLee, NP
 
dc.contributor.authorTsang, FH
 
dc.contributor.authorShek, FH
 
dc.contributor.authorMao, M
 
dc.contributor.authorDai, H
 
dc.contributor.authorZhang, C
 
dc.contributor.authorDong, S
 
dc.contributor.authorGuan, XY
 
dc.contributor.authorPoon, RTP
 
dc.contributor.authorLuk, JM
 
dc.date.accessioned2010-10-31T10:38:33Z
 
dc.date.available2010-10-31T10:38:33Z
 
dc.date.issued2010
 
dc.description.abstractUsing comparative proteomic and genomic approaches, the authors identified eukaryotic translation initiation factor 5A (eIF5A) as an oncofetal molecule highly abundant in mouse embryonic livers and human hepatocellular carcinoma (HCC) cell lines. To evaluate the oncogenic role and prognostic significance of eIF5A in HCC, we investigate the expression patterns of the two isoforms (eIF5A1 and eIF5A2) in a cohort of 258 HCC cases by cDNA microarray. Both eIF5A isoforms were expressed in the tumors, and clinically correlated eIF5A1 with more numbers of tumor nodules and eIF5A2 with tumor venous infiltration in HCC. In a separate cohort of 50 HCCs, high level of eIF5A2, but not eIF5A1, was associated with elevated levels of deoxyhypusine synthase and deoxyhypusine hydroxylase that catalyze post-translational hypusination of eIF5A protein. Interestingly, N1-guanyl-1,7-diaminoheptane (GC7), which is an inhibitor for the first step of eIF5A hypusination, was shown to significantly impair the cell proliferation and invasion of primary HCC cells (HepG2 and Hep3B). To further demonstrate the tumorigenic role associated with eIF5A, a drastic reduction of cell proliferation was associated with suppression of eIF5A2 by transfecting Hep3B, H2-P and H2-M HCC cells expressing high level of this isoform using small interfering RNA (siRNA) against eIF5A2. For these assays, a milder response was usually observed in normal hepatocyte cell line. Therefore, these findings suggest that eIF5A plays an important role in HCC tumorigenesis and metastasis, and targeting eIF5A hypusination by GC7 inhibitor or eIF5A2 by RNA interference (RNAi) may offer new therapeutic alternatives to HCC patients. © 2009 UICC.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 127 n. 4, p. 968-976 [How to Cite?]
DOI: http://dx.doi.org/10.1002/ijc.25100
 
dc.identifier.doihttp://dx.doi.org/10.1002/ijc.25100
 
dc.identifier.epage976
 
dc.identifier.hkuros175314
 
dc.identifier.isiWOS:000279971500024
Funding AgencyGrant Number
The University of Hong Kong
Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery
Funding Information:

Grant sponsor: This study was supported by a CRCG grant from The University of Hong Kong (to J.M.L.) and Sun Chieh Yeh Research Foundation for Hepatobiliary and Pancreatic Surgery (to R.T.P.)

 
dc.identifier.issn0020-7136
2013 Impact Factor: 5.007
 
dc.identifier.issue4
 
dc.identifier.openurl
 
dc.identifier.pmid19998337
 
dc.identifier.scopuseid_2-s2.0-77954743971
 
dc.identifier.spage968
 
dc.identifier.urihttp://hdl.handle.net/10722/124511
 
dc.identifier.volume127
 
dc.languageeng
 
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home
 
dc.publisher.placeUnited States
 
dc.relation.ispartofInternational Journal of Cancer
 
dc.relation.referencesReferences in Scopus
 
dc.rightsInternational Journal of Cancer. Copyright © John Wiley & Sons, Inc..
 
dc.rightsThis is a preprint of an article published in International Journal of Cancer, 2010, v. 127 n. 4, p. 968-976
 
dc.subject.meshCarcinoma, Hepatocellular - genetics - metabolism - pathology
 
dc.subject.meshLiver Neoplasms - genetics - metabolism - pathology
 
dc.subject.meshPeptide Initiation Factors - antagonists and inhibitors - genetics - metabolism
 
dc.subject.meshRNA-Binding Proteins - antagonists and inhibitors - genetics - metabolism
 
dc.subject.meshTumor Markers, Biological - genetics - metabolism
 
dc.subjecteIF5A
 
dc.subjectHepatocellular carcinoma
 
dc.subjectHypusination
 
dc.subjectOncofetal molecule
 
dc.subjectTargeted therapy
 
dc.titlePrognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. The University of Hong Kong
  2. Rosetta Inpharmatics LLC
  3. National University of Singapore
  4. Pfizer