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Article: MicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma

TitleMicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
Authors
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
Citation
Molecular Systems Biology, 2010, v. 6 How to Cite?
Abstract
Tumorigenesis 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.
Persistent Identifierhttp://hdl.handle.net/10722/125435
ISSN
2013 Impact Factor: 14.099
2013 SCImago Journal Rankings: 9.793
PubMed Central ID
ISI Accession Number ID
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.

References

 

Author Affiliations
  1. Sirna Therapeutics Inc.
  2. The University of Hong Kong
  3. Merck Research Laboratories
  4. Rosetta Inpharmatics LLC
  5. Merck & Co.
  6. University of Cambridge
  7. National University of Singapore
  8. Pfizer
DC FieldValueLanguage
dc.contributor.authorBurchard, Jen_HK
dc.contributor.authorZhang, Cen_HK
dc.contributor.authorLiu, AMen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorLee, NPYen_HK
dc.contributor.authorWong, KFen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorLam, BYen_HK
dc.contributor.authorFerguson, MDen_HK
dc.contributor.authorTokiwa, Gen_HK
dc.contributor.authorSmith, Ren_HK
dc.contributor.authorLeeson, Ben_HK
dc.contributor.authorBeard, Ren_HK
dc.contributor.authorLamb, JRen_HK
dc.contributor.authorLim, Len_HK
dc.contributor.authorMao, Men_HK
dc.contributor.authorDai, Hen_HK
dc.contributor.authorLuk, JMen_HK
dc.date.accessioned2010-10-31T11:31:16Z-
dc.date.available2010-10-31T11:31:16Z-
dc.date.issued2010en_HK
dc.identifier.citationMolecular Systems Biology, 2010, v. 6en_HK
dc.identifier.issn1744-4292en_HK
dc.identifier.urihttp://hdl.handle.net/10722/125435-
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.en_HK
dc.languageengen_HK
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/msb/index.htmlen_HK
dc.relation.ispartofMolecular Systems Biologyen_HK
dc.subjecthepatocellular carcinomaen_HK
dc.subjectmicroarrayen_HK
dc.subjectmiR-122en_HK
dc.subjectmitochondrialen_HK
dc.subjectsurvivalen_HK
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.titleMicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinomaen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1744-4292&volume=6&spage=402&epage=&date=2010&atitle=MicroRNA-122+as+a+regulator+of+mitochondrial+metabolic+gene+network+in+hepatocellular+carcinomaen_HK
dc.identifier.emailPoon, RTP: poontp@hku.hken_HK
dc.identifier.emailLee, NPY: nikkilee@hku.hken_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailLuk, JM: jmluk@hkucc.hku.hken_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityLee, NPY=rp00263en_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityLuk, JM=rp00349en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/msb.2010.58en_HK
dc.identifier.pmid20739924-
dc.identifier.pmcidPMC2950084-
dc.identifier.scopuseid_2-s2.0-77956249298en_HK
dc.identifier.hkuros182520en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956249298&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.spage402en_HK
dc.identifier.epage402-
dc.identifier.eissn1744-4292-
dc.identifier.isiWOS:000284527700003-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridBurchard, J=35586927300en_HK
dc.identifier.scopusauthoridZhang, C=7405492903en_HK
dc.identifier.scopusauthoridLiu, AM=36134439500en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridLee, NPY=7402722690en_HK
dc.identifier.scopusauthoridWong, KF=35081410800en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridLam, BY=7102023588en_HK
dc.identifier.scopusauthoridFerguson, MD=35208305500en_HK
dc.identifier.scopusauthoridTokiwa, G=36914025600en_HK
dc.identifier.scopusauthoridSmith, R=7410289032en_HK
dc.identifier.scopusauthoridLeeson, B=6507617735en_HK
dc.identifier.scopusauthoridBeard, R=15839248800en_HK
dc.identifier.scopusauthoridLamb, JR=7201524642en_HK
dc.identifier.scopusauthoridLim, L=7401517288en_HK
dc.identifier.scopusauthoridMao, M=7102960472en_HK
dc.identifier.scopusauthoridDai, H=7402206916en_HK
dc.identifier.scopusauthoridLuk, JM=7006777791en_HK
dc.identifier.citeulike7745353-

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