Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance

被引：34

作者：

Johnson, Katherine ^{[1
]}

Leary, Peter J. ^{[2
]}

Govaere, Olivier ^{[1
]}

Barter, Matthew J. ^{[3
]}

Charlton, Sarah H. ^{[3
]}

Cockell, Simon J. ^{[2
,3
]}

Tiniakos, Dina ^{[1
]}

Zatorska, Michalina ^{[1
]}

Bedossa, Pierre ^{[1
]}

Brosnan, M. Julia ^{[4
]}

Cobbold, Jeremy F. ^{[5
]}

Ekstedt, Mattias ^{[6
]}

Aithal, Guruprasad P. ^{[7
,8
]}

Clement, Karine ^{[9
,10
]}

Schattenberg, Joern M. ^{[11
]}

Boursier, Jerome ^{[12
]}

Ratziu, Vlad ^{[9
,10
]}

Bugianesi, Elisabetta ^{[13
]}

Anstee, Quentin M. ^{[1
,14
]}

Daly, Ann K. ^{[1
]}

机构：

[1] Newcastle Univ, Fac Med Sci, Translat & Clin Res Inst, Fourth Floor,William Leech Bldg,Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England

[2] Newcastle Univ, Fac Med Sci, Bioinformat Support Unit, Newcastle Upon Tyne, Tyne & Wear, England

[3] Newcastle Univ, Fac Med Sci, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England

[4] Pfizer Inc, Internal Med Res Unit, Cambridge, MA USA

[5] NIHR Oxford Biomed Res Ctr, John Radcliffe Hosp, Oxford Liver Unit, Oxford, England

[6] Linkoping Univ, Dept Hlth Med & Caring Sci, Div Diagnost & Specialist Med, Linkoping, Sweden

[7] Nottingham Univ Hosp NHS Trust, NIHR Nottingham Biomed Res Ctr, Nottingham, England

[8] Univ Nottingham, Nottingham, England

[9] Hop La Pitie Salpetriere, Inst Cardiometab & Nutr, Paris, France

[10] Assistance Publ Hop Paris, Paris, France

[11] Johannes Gutenberg Univ Mainz, Dept Med 1, Metab Liver Res Program, Univ Med Ctr, Mainz, Germany

[12] Angers Univ Hosp, Hepatol Dept, Angers, France

[13] Univ Turin, Dept Med Sci, Div Gastroenterol, Turin, Italy

[14] Newcastle Upon Tyne Hosp NHS Trust, Newcastle NIHR Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England

来源：

JHEP REPORTS | 2022年 / 4卷 / 02期

基金：

欧盟地平线“2020”;

关键词：

MicroRNA; Non-alcoholic fatty liver disease; Biomarker; Sequencing; SCORING SYSTEM; FIBROSIS; STEATOHEPATITIS; VALIDATION; EXPRESSION; ALGORITHM; ACID;

D O I：

10.1016/j.jhepr.2021.100409

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

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. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

引用

页数：12

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