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dc.contributor.authorFavaro, Een
dc.contributor.authorRamachandran, Aen
dc.contributor.authorMcCormick, Ren
dc.contributor.authorGee, Hen
dc.contributor.authorBlancher, Cen
dc.contributor.authorCrosby, Men
dc.contributor.authorDevlin, Cen
dc.contributor.authorBlick, Cen
dc.contributor.authorBuffa, Fen
dc.contributor.authorLi, J-Len
dc.contributor.authorVojnovic, Ben
dc.contributor.authorPires das Neves, Ren
dc.contributor.authorGlazer, Pen
dc.contributor.authorIborra, Fen
dc.contributor.authorIvan, Men
dc.contributor.authorRagoussis, Jen
dc.contributor.authorHarris, ALen
dc.date.accessioned2017-11-27T16:53:43Z
dc.date.available2017-11-27T16:53:43Z
dc.date.issued2010-04-26en
dc.identifier.urihttp://hdl.handle.net/10026.1/10316
dc.description.abstract

BACKGROUND: Hypoxia in cancers results in the upregulation of hypoxia inducible factor 1 (HIF-1) and a microRNA, hsa-miR-210 (miR-210) which is associated with a poor prognosis. METHODS AND FINDINGS: In human cancer cell lines and tumours, we found that miR-210 targets the mitochondrial iron sulfur scaffold protein ISCU, required for assembly of iron-sulfur clusters, cofactors for key enzymes involved in the Krebs cycle, electron transport, and iron metabolism. Down regulation of ISCU was the major cause of induction of reactive oxygen species (ROS) in hypoxia. ISCU suppression reduced mitochondrial complex 1 activity and aconitase activity, caused a shift to glycolysis in normoxia and enhanced cell survival. Cancers with low ISCU had a worse prognosis. CONCLUSIONS: Induction of these major hallmarks of cancer show that a single microRNA, miR-210, mediates a new mechanism of adaptation to hypoxia, by regulating mitochondrial function via iron-sulfur cluster metabolism and free radical generation.

en
dc.format.extente10345 - ?en
dc.languageengen
dc.language.isoengen
dc.subjectCell Line, Tumoren
dc.subjectCitric Acid Cycleen
dc.subjectElectron Transport Complex Ien
dc.subjectFree Radicalsen
dc.subjectHumansen
dc.subjectHypoxiaen
dc.subjectHypoxia-Inducible Factor 1, alpha Subuniten
dc.subjectIron-Sulfur Proteinsen
dc.subjectMicroRNAsen
dc.subjectMitochondriaen
dc.subjectNeoplasmsen
dc.subjectPrognosisen
dc.titleMicroRNA-210 regulates mitochondrial free radical response to hypoxia and krebs cycle in cancer cells by targeting iron sulfur cluster protein ISCU.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/20436681en
plymouth.issue4en
plymouth.volume5en
plymouth.publication-statusPublished onlineen
plymouth.journalPLoS Oneen
dc.identifier.doi10.1371/journal.pone.0010345en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine/UoA01 Clinical Medicine
dc.publisher.placeUnited Statesen
dcterms.dateAccepted2010-03-29en
dc.identifier.eissn1932-6203en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1371/journal.pone.0010345en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2010-04-26en
rioxxterms.typeJournal Article/Reviewen


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