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Article: MicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
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TitleMicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
 
AuthorsBurchard, J1 4
Zhang, C4 3
Liu, AM2 7
Poon, RTP2
Lee, NPY2
Wong, KF2 7
Sham, PC2
Lam, BY6
Ferguson, MD4 3
Tokiwa, G5 4
Smith, R4 3
Leeson, B4
Beard, R4
Lamb, JR8 4
Lim, L1 4
Mao, M8 4
Dai, H4 3
Luk, JM7 2
 
Keywordshepatocellular carcinoma
microarray
miR-122
mitochondrial
survival
 
Issue Date2010
 
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/msb/index.html
 
CitationMolecular Systems Biology, 2010, v. 6 [How to Cite?]
DOI: http://dx.doi.org/10.1038/msb.2010.58
 
AbstractTumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)-gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122-controlled genes and impairment of mitochondrial metabolism. In conclusion, miR-122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients. © 2010 EMBO and Macmillan Publishers Limited.
 
ISSN1744-4292
2013 Impact Factor: 14.099
2013 SCImago Journal Rankings: 9.793
 
DOIhttp://dx.doi.org/10.1038/msb.2010.58
 
PubMed Central IDPMC2950084
 
ISI Accession Number IDWOS:000284527700003
Funding AgencyGrant Number
Hong Kong University
NMRC Block Vote
National University of Singapore
Funding Information:

The work is partly supported by the small project fund of the Hong Kong University, NMRC Block Vote, and Start-up fund of the National University of Singapore to JML. We gratefully acknowledge Sheung-Tat Fan of Queen Mary Hospital for his expert clinical advice in HCC, Douglas Bassett and Alan Sachs of Merck and Co., Inc. for guidance and support of these studies, and C Frank Bennett and Christy Esau of Isis Pharmaceuticals, Inc. for provision of the anti-miR-122-treated mouse liver samples and for helpful discussions. In addition, we thank Ke Hao, Tao Xie, Steven Bartz, Walter Strapps, Lyndon Mitnaul, Luiz Miguel Camargo, Robert Phillips, Peter Shaw, Eric Schadt, Peter Linsley, and Carolyn Buser-Dopner of Merck and Co., Inc. for scientific input and helpful discussions.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorBurchard, J
 
dc.contributor.authorZhang, C
 
dc.contributor.authorLiu, AM
 
dc.contributor.authorPoon, RTP
 
dc.contributor.authorLee, NPY
 
dc.contributor.authorWong, KF
 
dc.contributor.authorSham, PC
 
dc.contributor.authorLam, BY
 
dc.contributor.authorFerguson, MD
 
dc.contributor.authorTokiwa, G
 
dc.contributor.authorSmith, R
 
dc.contributor.authorLeeson, B
 
dc.contributor.authorBeard, R
 
dc.contributor.authorLamb, JR
 
dc.contributor.authorLim, L
 
dc.contributor.authorMao, M
 
dc.contributor.authorDai, H
 
dc.contributor.authorLuk, JM
 
dc.date.accessioned2010-10-31T11:31:16Z
 
dc.date.available2010-10-31T11:31:16Z
 
dc.date.issued2010
 
dc.description.abstractTumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)-gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122-controlled genes and impairment of mitochondrial metabolism. In conclusion, miR-122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients. © 2010 EMBO and Macmillan Publishers Limited.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationMolecular Systems Biology, 2010, v. 6 [How to Cite?]
DOI: http://dx.doi.org/10.1038/msb.2010.58
 
dc.identifier.citeulike7745353
 
dc.identifier.doihttp://dx.doi.org/10.1038/msb.2010.58
 
dc.identifier.eissn1744-4292
 
dc.identifier.epage402
 
dc.identifier.hkuros182520
 
dc.identifier.isiWOS:000284527700003
Funding AgencyGrant Number
Hong Kong University
NMRC Block Vote
National University of Singapore
Funding Information:

The work is partly supported by the small project fund of the Hong Kong University, NMRC Block Vote, and Start-up fund of the National University of Singapore to JML. We gratefully acknowledge Sheung-Tat Fan of Queen Mary Hospital for his expert clinical advice in HCC, Douglas Bassett and Alan Sachs of Merck and Co., Inc. for guidance and support of these studies, and C Frank Bennett and Christy Esau of Isis Pharmaceuticals, Inc. for provision of the anti-miR-122-treated mouse liver samples and for helpful discussions. In addition, we thank Ke Hao, Tao Xie, Steven Bartz, Walter Strapps, Lyndon Mitnaul, Luiz Miguel Camargo, Robert Phillips, Peter Shaw, Eric Schadt, Peter Linsley, and Carolyn Buser-Dopner of Merck and Co., Inc. for scientific input and helpful discussions.

 
dc.identifier.issn1744-4292
2013 Impact Factor: 14.099
2013 SCImago Journal Rankings: 9.793
 
dc.identifier.openurl
 
dc.identifier.pmcidPMC2950084
 
dc.identifier.pmid20739924
 
dc.identifier.scopuseid_2-s2.0-77956249298
 
dc.identifier.spage402
 
dc.identifier.urihttp://hdl.handle.net/10722/125435
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/msb/index.html
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofMolecular Systems Biology
 
dc.relation.referencesReferences in Scopus
 
dc.subject.meshCarcinoma, Hepatocellular - genetics
 
dc.subject.meshGene Expression Regulation, Neoplastic
 
dc.subject.meshGene Regulatory Networks - genetics
 
dc.subject.meshLiver Neoplasms - genetics
 
dc.subject.meshMicroRNAs - genetics - metabolism
 
dc.subjecthepatocellular carcinoma
 
dc.subjectmicroarray
 
dc.subjectmiR-122
 
dc.subjectmitochondrial
 
dc.subjectsurvival
 
dc.titleMicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
 
dc.typeArticle
 
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Author Affiliations
  1. Sirna Therapeutics Inc.
  2. The University of Hong Kong
  3. Merck Research Laboratories
  4. Rosetta Inpharmatics LLC
  5. Merck &amp; Co.
  6. University of Cambridge
  7. National University of Singapore
  8. Pfizer