Article: Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma
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- Publisher Website: 10.1002/ijc.25100
- Scopus: eid_2-s2.0-77954743971
- PMID: 19998337
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| Title | Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Lee, NP1 Tsang, FH1 Shek, FH1 Mao, M2 4 Dai, H2 Zhang, C2 Dong, S1 Guan, XY1 Poon, RTP1 Luk, JM1 3 | ||||||
| Keywords | eIF5A Hepatocellular carcinoma Hypusination Oncofetal molecule Targeted therapy | ||||||
| Issue Date | 2010 | ||||||
| Publisher | John 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?] DOI: http://dx.doi.org/10.1002/ijc.25100 | ||||||
| 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. | ||||||
| ISSN | 0020-7136 2011 Impact Factor: 5.444 2011 SCImago Journal Rankings: 0.620 | ||||||
| DOI | http://dx.doi.org/10.1002/ijc.25100 | ||||||
| ISI Accession Number ID | WOS:000279971500024
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 | References in Scopus |
| dc.contributor.author | Lee, NP | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | Tsang, FH | ||||||
| dc.contributor.author | Shek, FH | ||||||
| dc.contributor.author | Mao, M | ||||||
| dc.contributor.author | Dai, H | ||||||
| dc.contributor.author | Zhang, C | ||||||
| dc.contributor.author | Dong, S | ||||||
| dc.contributor.author | Guan, XY | ||||||
| dc.contributor.author | Poon, RTP | ||||||
| dc.contributor.author | Luk, JM | ||||||
| dc.date.accessioned | 2010-10-31T10:38:33Z | ||||||
| dc.date.available | 2010-10-31T10:38:33Z | ||||||
| dc.date.issued | 2010 | ||||||
| dc.description.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. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | International 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.doi | http://dx.doi.org/10.1002/ijc.25100 | ||||||
| dc.identifier.epage | 976 | ||||||
| dc.identifier.hkuros | 175314 | ||||||
| dc.identifier.isi | WOS:000279971500024
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.issn | 0020-7136 2011 Impact Factor: 5.444 2011 SCImago Journal Rankings: 0.620 | ||||||
| dc.identifier.issue | 4 | ||||||
| dc.identifier.openurl | | ||||||
| dc.identifier.pmid | 19998337 | ||||||
| dc.identifier.scopus | eid_2-s2.0-77954743971 | ||||||
| dc.identifier.spage | 968 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/124511 | ||||||
| dc.identifier.volume | 127 | ||||||
| dc.language | eng | ||||||
| dc.publisher | John Wiley & Sons, Inc.. The Journal's web site is located at http://www3.interscience.wiley.com/journal/29331/home | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | International Journal of Cancer | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | International Journal of Cancer. Copyright © John Wiley & Sons, Inc.. | ||||||
| dc.rights | This is a preprint of an article published in International Journal of Cancer, 2010, v. 127 n. 4, p. 968-976 | ||||||
| dc.subject.mesh | Carcinoma, Hepatocellular - genetics - metabolism - pathology | ||||||
| dc.subject.mesh | Liver Neoplasms - genetics - metabolism - pathology | ||||||
| dc.subject.mesh | Peptide Initiation Factors - antagonists and inhibitors - genetics - metabolism | ||||||
| dc.subject.mesh | RNA-Binding Proteins - antagonists and inhibitors - genetics - metabolism | ||||||
| dc.subject.mesh | Tumor Markers, Biological - genetics - metabolism | ||||||
| dc.subject | eIF5A | ||||||
| dc.subject | Hepatocellular carcinoma | ||||||
| dc.subject | Hypusination | ||||||
| dc.subject | Oncofetal molecule | ||||||
| dc.subject | Targeted therapy | ||||||
| dc.title | Prognostic significance and therapeutic potential of eukaryotic translation initiation factor 5A (eIF5A) in hepatocellular carcinoma | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Rosetta Inpharmatics LLC
- National University of Singapore
- Pfizer