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Profile of plasma microRNAs as a potential biomarker of Wilson's disease
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Journal Article
Profile of plasma microRNAs as a potential biomarker of Wilson's disease
2024
Overview
Background Wilson's disease (WD) is a rare condition resulting from autosomal recessive mutations in ATP7B, a copper transporter, manifesting with hepatic, neurological, and psychiatric symptoms. Timely diagnosis and appropriate treatment yield a positive prognosis, while delayed identification and/or insufficient therapy lead to a poor outcome. Our aim was to establish a prognostic method for WD by characterising biomarkers based on circulating microRNAs. Methods We conducted investigations across three cohorts: discovery, validation (comprising unrelated patients), and follow-up (revisiting the discovery cohort 3 years later). All groups were compared to age- and gender-matched controls. Plasma microRNAs were analysed via RNA sequencing in the discovery cohort and subsequently validated using quantitative PCR in all three cohorts. To assess disease progression, we examined the microRNA profile in Atp7b−/− mice, analysing serum samples from 6 to 44 weeks of age and liver samples at three time points: 20, 30, and 40 weeks of age. Results In patients, elevated levels of the signature microRNAs (miR-122-5p, miR-192-5p, and miR-885-5p) correlated with serum activities of aspartate transaminase, alanine aminotransferase and gamma-glutamyl transferase. In Atp7b−/− mice, levels of miR-122-5p and miR-192-5p (miR-885-5p lacking a murine orthologue) increased from 12 weeks of age in serum, while exhibiting fluctuations in the liver, possibly attributable to hepatocyte regenerative capacity post-injury and the release of hepatic microRNAs into the bloodstream. Conclusions The upregulation of the signature miR-122-5p, miR-192-5p, and miR-885-5p in patients and their correlation with liver disease progression in WD mice support their potential as biomarkers of WD.
Publisher
Springer Nature Singapore,Springer,Springer Nature B.V
Subject
/ Adult
/ Alanine Transaminase - blood
/ Animals
/ Aspartate Aminotransferases - blood
/ Circulating MicroRNA - blood
/ Circulating MicroRNA - genetics
/ Copper-Transporting ATPases - genetics
/ Ethylenediaminetetraacetic acid
/ Female
/ gamma-Glutamyltransferase - blood
/ Hepatolenticular Degeneration - blood
/ Hepatolenticular Degeneration - diagnosis
/ Hepatolenticular Degeneration - genetics
/ Humans
/ Liver
/ Male
/ Medicine
/ Mice
/ MicroRNA
/ miRNA
/ Original ―Liver, Pancreas, and Biliary Tract
/ Pancreas
