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Article: Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma

TitlePrognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma
Authors
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
Citation
International Journal Of Cancer, 2010, v. 127 n. 4, p. 968-976 How to Cite?
Abstract
Using 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.
Persistent Identifierhttp://hdl.handle.net/10722/124511
ISSN
2013 Impact Factor: 5.007
ISI Accession Number ID
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.)

References

 

Author Affiliations
  1. The University of Hong Kong
  2. Rosetta Inpharmatics LLC
  3. National University of Singapore
  4. Pfizer
DC FieldValueLanguage
dc.contributor.authorLee, NPen_HK
dc.contributor.authorTsang, FHen_HK
dc.contributor.authorShek, FHen_HK
dc.contributor.authorMao, Men_HK
dc.contributor.authorDai, Hen_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorDong, Sen_HK
dc.contributor.authorGuan, XYen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2010-10-31T10:38:33Z-
dc.date.available2010-10-31T10:38:33Z-
dc.date.issued2010en_HK
dc.identifier.citationInternational Journal Of Cancer, 2010, v. 127 n. 4, p. 968-976en_HK
dc.identifier.issn0020-7136en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124511-
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.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/homeen_HK
dc.relation.ispartofInternational Journal of Canceren_HK
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.subjecteIF5Aen_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectHypusinationen_HK
dc.subjectOncofetal moleculeen_HK
dc.subjectTargeted therapyen_HK
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.titlePrognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0020-7136&volume=127&issue=4&spage=968&epage=976&date=2010&atitle=Prognostic+significance+and+therapeutic+potential+of+eukaryotic+translation+initiation+factor+5A+(eIF5A)+in+hepatocellular+carcinomaen_HK
dc.identifier.emailLee, NP: nikkilee@hku.hken_HK
dc.identifier.emailGuan, XY: xyguan@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityLee, NP=rp00263en_HK
dc.identifier.authorityGuan, XY=rp00454en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/ijc.25100en_HK
dc.identifier.pmid19998337-
dc.identifier.scopuseid_2-s2.0-77954743971en_HK
dc.identifier.hkuros175314en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77954743971&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume127en_HK
dc.identifier.issue4en_HK
dc.identifier.spage968en_HK
dc.identifier.epage976en_HK
dc.identifier.isiWOS:000279971500024-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLee, NP=7402722690en_HK
dc.identifier.scopusauthoridTsang, FH=36895782100en_HK
dc.identifier.scopusauthoridShek, FH=36094922800en_HK
dc.identifier.scopusauthoridMao, M=7102960472en_HK
dc.identifier.scopusauthoridDai, H=7402206916en_HK
dc.identifier.scopusauthoridZhang, C=9747304800en_HK
dc.identifier.scopusauthoridDong, S=35788109500en_HK
dc.identifier.scopusauthoridGuan, XY=7201463221en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK

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