Genetic architecture and regulatory impact on hepatic microRNA expression linked to immune and metabolic traits

Abstract

Regulation of microRNA (miRNA) expression contributes to a wide range of target gene expression and phenotypes. The miRNA expression in the liver, the central metabolic organ, was examined in 209 pigs, and integrated with haematological and clinical biomarkers of metabolic and overall health, mRNA-target expression levels and single-nucleotide polymorphism (SNP) genotypes. The expression levels of 426 miRNA species correlated with plasma haematological or biochemical traits (r² = |0.19–0.45|, false discovery rate < 5%). Pairs of these miRNAs and their predicted target mRNAs showing expressing levels associated with the identical traits were examined to understand how immune and metabolic traits are affected by miRNA-mediated regulatory networks derived by mapping miRNA abundance as an expression quantitative trait. In total, 221 miRNA-expression-QTL correspond to 164 SNPs and 108 miRNAs, including miR-34a, miR-30e, miR-148-3p, miR-204, miR-181-5p, miR-143-5p and let-7 g that also correlate with the biomarkers. Sixty-one SNPs were simultaneously associated with 29 miRNA and 41 mRNA species. The expression levels of 13 out of 29 miRNA were correlated with one of the biochemical or haematological traits. For example, the expression levels of miR-34a were correlated with serum phosphorus and cholesterin levels; miR-204, miR-15a and miR-16b were correlated with triglyceride. For haematological traits, the expression levels of miR-652 and miR-204 were correlated with the mean corpuscular haemoglobin concentration, and the expression of miR-143 was correlated with plateletcrit. Pleiotropic association analyses revealed genetic links between mRNA and miRNA on SSC6 for miR-34a, SSC9 for miR-708 and SSC14 for miR-652. Our analysis of miRNA and mRNA transcript profiles, their correlation with clinically important plasma parameters of hepatic functions as well as information on their genetic regulation provide novel regulatory networks and potential new biomarkers for immune and metabolic traits.

Identification of the Key Molecular Drivers of Phosphorus Utilization Based on Host miRNA-mRNA and Gut Microbiome Interactions

“…Five miRNAs of the let-7 family belong to the molecular panel for PU. Previous studies found that the expression of the let-7 family correlated significantly with glucose levels and regulates glucose metabolism [55,56]. IGSF10 was negatively correlated and predicted as a target of miR-148a-3p and miR-142a-5p in this study.…”

Peripheral blood microRNA levels in females with cocaine use disorder

“…In addition to their role in cocaine-induced neuroplasticity, both miRNAs were predicted to target genes implicated with metabolic processes, with a more pronounced list of hits associated with miR-181 functioning (25%). Previous studies have suggested a role for miR-124 and miR-181 on the regulation of metabolic traits in fat tissues and in the liver (Pan, Jing, Qiao et al, 2018;Ponsuksili, Trakooljul, Hadlich et al, 2017). Interestingly, the systemic pathophysiology of CUD includes several metabolic alterations.…”

Insight into genetic regulation of miRNA in mouse brain

“…In a marker regression analysis, expression is regressed onto the genotype. To be consistent with the literature [14, 16, 20] and the controlled nature of recombinant inbred mice (all of which are male), no covariates were included in the model. 95% Bayes’ credible intervals were also calculated using R/qtl.…”