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dc.creatorJohnson, Katherinees
dc.creatorLeary, Peter J.es
dc.creatorGovaere, Olivieres
dc.creatorBarter, Matthew J.es
dc.creatorCharlton, Sarah H.es
dc.creatorCockell, Simon J.es
dc.creatorRomero Gómez, Manueles
dc.creatorMiller, Melissaes
dc.date.accessioned2022-09-28T13:36:35Z
dc.date.available2022-09-28T13:36:35Z
dc.date.issued2022
dc.identifier.citationJohnson, K., Leary, P.J., Govaere, O., Barter, M.J., Charlton, S.H., Cockell, S.J.,...,Miller, M. (2022). Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance. JHEP Reports, 4 (2), 1-11.
dc.identifier.issn2589-5559es
dc.identifier.urihttps://hdl.handle.net/11441/137430
dc.description.abstractBackground & Aims Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages. Methods We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls). miRNA libraries generated by HTG EdgeSeq were sequenced by Illumina NextSeq. Selected serum miRNAs were profiled in 372 additional cases with NAFLD and 15 population controls by quantitative reverse transcriptase PCR. Results Levels of 275 miRNAs differed between cases and population controls. Fewer differences were seen within individual NAFLD stages, but miR-193a-5p consistently showed increased levels in all comparisons. Relative to NAFL/non-alcoholic steatohepatitis (NASH) with mild fibrosis (stage 0/1), 3 miRNAs (miR-193a-5p, miR-378d, and miR378d) were increased in cases with NASH and clinically significant fibrosis (stages 2–4), 7 (miR193a-5p, miR-378d, miR-378e, miR-320b, miR-320c, miR-320d, and miR-320e) increased in cases with NAFLD activity score (NAS) 5–8 compared with lower NAS, and 3 (miR-193a-5p, miR-378d, and miR-378e) increased but 1 (miR-19b-3p) decreased in steatosis, activity, and fibrosis (SAF) activity score 2–4 compared with lower SAF activity. The significant findings for miR-193a-5p were replicated in the additional cohort with NAFLD. Studies in Hep G2 cells showed that following palmitic acid treatment, miR-193a-5p expression decreased significantly. Gene targets for miR-193a-5p were investigated in liver RNAseq data for a case subgroup (n = 80); liver GPX8 levels correlated positively with serum miR-193a-5p. Conclusions Serum miR-193a-5p levels correlate strongly with NAFLD activity grade and fibrosis stage. MiR-193a-5p may have a role in the hepatic response to oxidative stress and is a potential clinically tractable circulating biomarker for progressive NAFLD.es
dc.formatapplication/pdfes
dc.format.extent12 p.es
dc.language.isoenges
dc.publisherElsevier BVes
dc.relation.ispartofJHEP Reports, 4 (2), 1-11.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMicroRNAes
dc.subjectNon-alcoholic fatty liver diseasees
dc.subjectBiomarkeres
dc.subjectSequencinges
dc.titleIncreased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevancees
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/publishedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.contributor.affiliationUniversidad de Sevilla. Departamento de Medicinaes
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S2589555921001853?via%3Dihubes
dc.identifier.doi10.1016/j.jhepr.2021.100409es
dc.journaltitleJHEP Reportses
dc.publication.volumen4es
dc.publication.issue2es
dc.publication.initialPage1es
dc.publication.endPage11es

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