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dc.contributor.authorBurchard, Julja
dc.contributor.authorZhang, Chunsheng
dc.contributor.authorLiu, Angela M
dc.contributor.authorPoon, Ronnie TP
dc.contributor.authorLee, Nikki PY
dc.contributor.authorWong, Kwong-Fai
dc.contributor.authorSham, Pak C
dc.contributor.authorLam, Brian
dc.contributor.authorFerguson, Mark D
dc.contributor.authorTokiwa, George
dc.contributor.authorSmith, Ryan
dc.contributor.authorLeeson, Brendan
dc.contributor.authorBeard, Rebecca
dc.contributor.authorLamb, John R
dc.contributor.authorLim, Lee
dc.contributor.authorMao, Mao
dc.contributor.authorDai, Hongyue
dc.contributor.authorLuk, John M
dc.date.accessioned2017-08-08T11:27:59Z
dc.date.available2017-08-08T11:27:59Z
dc.date.issued2010-08-24
dc.identifier.issn1744-4292
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/266001
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.
dc.format.mediumPrint
dc.languageeng
dc.publisherEMBO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectLiver
dc.subjectCell Line, Tumor
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectHumans
dc.subjectMice
dc.subjectCarcinoma, Hepatocellular
dc.subjectLiver Neoplasms
dc.subjectMicroRNAs
dc.subjectRNA, Messenger
dc.subjectSurvival Analysis
dc.subjectReproducibility of Results
dc.subjectGene Expression Profiling
dc.subjectSignal Transduction
dc.subjectDown-Regulation
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectUp-Regulation
dc.subjectSequence Homology, Nucleic Acid
dc.subjectEnergy Metabolism
dc.subjectGenes, Mitochondrial
dc.subjectGene Regulatory Networks
dc.titlemicroRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma.
dc.typeArticle
prism.publicationDate2010
prism.publicationNameMol Syst Biol
prism.startingPage402
prism.volume6
dc.identifier.doi10.17863/CAM.10877
dcterms.dateAccepted2010-06-29
rioxxterms.versionofrecord10.1038/msb.2010.58
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2010-08
dc.contributor.orcidLam, Brian [0000-0002-3638-9025]
dc.identifier.eissn1744-4292
rioxxterms.typeJournal Article/Review
cam.issuedOnline2010-08-24


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International