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RESEARCH PRODUCT
Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
Raluca PaisRachel OstroffStephen HarrisonLars Friis MikkelsenElisabeth ErhardtsenSudha ShankarKimmo PorthanJérôme BoursierAntonia SinisiMichael KalutkiewiczSven FrancqueMiljen MarticVanessa PellegrinelliPhil N. NewsomeGuido HanauerHannele Yki-järvinenRebecca DarlayJoel MyersCarla YunisSalvatore PettaMette Skalshøi KjærPablo OrtizAnn K. DalyJames H. ClarkDina TiniakosYasaman ValiHadi ZafarmandMatej OrešičMaurizio ParolaEstelle SandtLori L. JenningsMatt KellyTuulia HyötyläinenDetlef SchuppanCéline FournierChiara RossoDiane E. ShevellMaria Manuela ToniniPaul HockingsAidan McglincheySalma AkhtarMette Juul FiskerMorten KarsdalDiane WhalleyMelissa R. MillerAldo TrylesinskiMattias EkstedtStefan NeubauerJeremy M. PalmerPartho SenMichael PavlidesPer QvistIsabel FernándezLuca MieleFabio MarraStergios KechagiasRichard TorstensonKatherine JohnsonJean-françois DufourElisabetta BugianesiM. Julia BrosnanGeorge V. PapatheodoridisKay M. PepinDaniel Guldager Kring RasmussenHenrik LandgrenRachel QueenSimon CockellMichael AllisonPatrick M.m. BossuytRocío Gallego-duránChristian RosenquistLeigh AlexanderElizabeth ShumbayawondaMichele VaccaAntonio Vidal-puigDavid WennRémy HanfOscar MilletMichalina ZatorskaR. MyersJosé M. MatoJenny LeeTheresa TuthillJames TwissRamy YounesPeter LearyLynda DowardKristy WondersGuruprasad P AithalSarah CharltonVlad RatziuCecília M. P. RodriguesChristian TrautweinHelena Cortez-pintoGideon HoMatt J. BarterJudith ErtleJörn M. SchattenbergMaria-magdalena BalpYang-lin LiuClifford A. BrassOlivier GovaereAmalia GastaldelliSergio Rodriguez CuencaPierre ChaumatFiona OakleyLuca ValentiSimon J. CockellSaskia W.c. Van MilFerenc E. MózesAndreas GeierTimothy HardyPierre BedossaAndrea DennisRichard L. EhmanCharlotte ErpicumKarine ClémentJeremy F. L. CobboldChristopher P. DayRajarshi BanerjeeManuel Romero-gómezQuentin M. AnsteeAdriaan G. HolleboomHeather J. CordellKevin L. DuffinDiana Julie Leemingsubject
SCORING SYSTEMCPM counts per millionAUROC area under the receiver operating characteristicRC799-869AST aspartate aminotransferaseMicroRNA; Non-alcoholic fatty liver disease; Biomarker; SequencingTGF-β transforming growth factor-betaGastroenterologySTEATOHEPATITISLiver disease0302 clinical medicineFibrosismiRNA microRNAlogFC log2 fold changeFIBROSISImmunology and AllergySequencing0303 health scienceseducation.field_of_studyNAS NAFLD activity scoremedicine.diagnostic_testFatty liverGastroenterologyGTEx Genotype-Tissue ExpressionMicroRNADiseases of the digestive system. Gastroenterology3. Good healthReal-time polymerase chain reactionBiomarker MicroRNA Non-alcoholic fatty liver disease SequencingLiver biopsyACIDBiomarker (medicine)030211 gastroenterology & hepatologyLife Sciences & BiomedicineResearch ArticleEXPRESSIONmedicine.medical_specialtyNAFLD non-alcoholic fatty liver diseaseNASH non-alcoholic steatohepatitisPopulationGastroenterology and HepatologySAF steatosis–activity–fibrosisVALIDATIONER endoplasmic reticulum03 medical and health sciencescDNA complementary DNAInternal medicineALT alanine aminotransferaseGastroenterologiInternal MedicinemedicineNAFL non-alcoholic fatty liverALGORITHMFIB-4 fibrosis-4education030304 developmental biologyPCA principal component analysisScience & TechnologyGastroenterology & HepatologyHepatologybusiness.industryBiomarkerFC fold changemedicine.diseaseBiomarker; MicroRNA; Non-alcoholic fatty liver disease; Sequencingdigestive system diseasesFLIP fatty liver inhibition of progressionCt cycle thresholdSteatosisqPCR quantitative PCRbusinessNon-alcoholic fatty liver diseasedescription
Background & 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. Lay summary MicroRNAs (miRNAs) are small pieces of nucleic acid that may turn expression of genes on or off. These molecules can be detected in the blood circulation, and their levels in blood may change in liver disease including non-alcoholic fatty liver disease (NAFLD). To see if we could detect specific miRNA associated with advanced stages of NAFLD, we carried out miRNA sequencing in a group of 183 patients with NAFLD of varying severity together with 10 population controls. We found that a number of miRNAs showed changes, mainly increases, in serum levels but that 1 particular miRNA miR-193a-5p consistently increased. We confirmed this increase in a second group of cases with NAFLD. Measuring this miRNA in a blood sample may be a useful way to determine whether a patient has advanced NAFLD without an invasive liver biopsy.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2022-02-01 |