Back to Search
Start Over
Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance
- Source :
- JHEP Reports, 4(2):100409. Elsevier, JHEP Reports, JHEP Reports, Vol 4, Iss 2, Pp 100409-(2022), JHEP reports 4(2), 100409 (2022). doi:10.1016/j.jhepr.2021.100409
- Publication Year :
- 2022
-
Abstract
- 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.<br />Graphical abstract<br />Highlights • Serum miRNA was sequenced in 183 NAFLD cases of varying severity and 10 population controls. • Plasma levels of miR-193a-5p were significantly increased in patients with advanced fibrosis, high NAS scores, or high SAF scores. • Other miRNAs including miR378d and miR378e were also significantly increased in certain comparisons. • The findings for miR-193a-5p were replicated in a cohort of 372 additional NAFLD cases.
- Subjects :
- SCORING SYSTEM
CPM, counts per million
AUROC, area under the receiver operating characteristic
RC799-869
AST, aspartate aminotransferase
MicroRNA
Non-alcoholic fatty liver disease
Biomarker
Sequencing
TGF-β, transforming growth factor-beta
Gastroenterology
STEATOHEPATITIS
Liver disease
0302 clinical medicine
Fibrosis
miRNA, microRNA
logFC, log2 fold change
FIBROSIS
Immunology and Allergy
0303 health sciences
education.field_of_study
NAS, NAFLD activity score
medicine.diagnostic_test
Fatty liver
GTEx, Genotype-Tissue Expression
Diseases of the digestive system. Gastroenterology
3. Good health
Real-time polymerase chain reaction
Biomarker, MicroRNA, Non-alcoholic fatty liver disease, Sequencing
Liver biopsy
ACID
Biomarker (medicine)
030211 gastroenterology & hepatology
Life Sciences & Biomedicine
Research Article
EXPRESSION
medicine.medical_specialty
NAFLD, non-alcoholic fatty liver disease
NASH, non-alcoholic steatohepatitis
Population
Gastroenterology and Hepatology
SAF, steatosis–activity–fibrosis
VALIDATION
ER, endoplasmic reticulum
03 medical and health sciences
cDNA, complementary DNA
Internal medicine
ALT, alanine aminotransferase
Gastroenterologi
Internal Medicine
medicine
NAFL, non-alcoholic fatty liver
ALGORITHM
FIB-4, fibrosis-4
education
030304 developmental biology
PCA, principal component analysis
Science & Technology
Gastroenterology & Hepatology
Hepatology
business.industry
FC, fold change
medicine.disease
digestive system diseases
FLIP, fatty liver inhibition of progression
Ct, cycle threshold
Steatosis
qPCR, quantitative PCR
business
Subjects
Details
- Language :
- English
- ISSN :
- 25895559
- Database :
- OpenAIRE
- Journal :
- JHEP Reports, 4(2):100409. Elsevier, JHEP Reports, JHEP Reports, Vol 4, Iss 2, Pp 100409-(2022), JHEP reports 4(2), 100409 (2022). doi:10.1016/j.jhepr.2021.100409
- Accession number :
- edsair.doi.dedup.....1c39a3a5921e0d464a7b2b93c40ef52c