Comprehensive analysis of blood cells and plasma identifies tissue-specific miRNAs as potential novel circulating biomarkers in cattle

Jason Ioannidis,F Xavier Donadeu

doi:10.1186/s12864-018-4646-5

Jason Ioannidis, F Xavier Donadeu

Open Access

https://doi.org/10.1186/s12864-018-4646-5

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Journal: BMC Genomics	Publication Date: Apr 10, 2018
Citations: 26	License type: open-access

Affiliation: Roslin Institute, University of Edinburgh

Abstract

BackgroundThe potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans. In addition, circulating miRNA biomarkers offer significant potential towards improving the productivity of livestock species, however, such potential has been hampered by the absence of information on the nature and source of circulating miRNA populations in these species. In addition, many miRNAs originally proposed as robust biomarkers of a particular tissue or disease in humans have been later shown not to be tissue specific and thus to actually have limited biomarker utility. In this study, we comprehensively analysed miRNA profiles in plasma and cell fractions of blood from cattle with the aim to identify tissue-derived miRNAs which may be useful as biomarkers of tissue function in this important food animal species.ResultsUsing small RNA sequencing, we identified 92 miRNAs with significantly higher expression in plasma compared to paired blood cell samples (n = 4 cows). Differences in miRNA levels between plasma and cell fractions were validated for eight out of 10 miRNAs using RT-qPCR (n = 10 cows). Among miRNAs found to be enriched in plasma, we confirmed miR-122 (liver), miR-133a (muscle) and miR-215 (intestine) to be tissue-enriched, as reported for other species. Profiling of additional miRNAs across different tissues identified the human homologue, miR-802, as highly enriched specifically in liver.ConclusionsThese results provide novel information on the source of bovine circulating miRNAs and could significantly facilitate the identification of production-relevant tissue biomarkers in livestock. In particular, miR-802, a circulating miRNA not previously identified in cattle, can reportedly regulate insulin sensitivity and lipid metabolism, and thus could potentially provide a specific biomarker of liver function, a key parameter in the context of post-partum negative energy balance in dairy cows.

Highlights

The potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans
Using next-generation sequencing, we provide a list of potential tissue-enriched miRNAs in circulation including miR-802, a previously uncharacterised bovine liver-specific miRNA which may prove useful as a disease biomarker in high-producing cows
Small RNA sequencing of different blood fractions To determine the relative abundance of miRNAs in different blood compartments, we sequenced miRNAs in paired blood plasma and cell fractions from four cows

Summary

Introduction

The potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans. Many miRNAs originally proposed as robust biomarkers of a particular tissue or disease in humans have been later shown not to be tissue specific and to have limited biomarker utility. The value of circulating miRNAs as diagnostic biomarkers has been shown in relation to cancer (e.g. miR-21, miR-20, miR-221 [10, 11]), cardiovascular disease (miR-1, miR-133a [12]), liver disease (miR-122 [13]) and diabetes (miR-375 and miR-34 [14]), among many other human pathologies and physiological processes including pregnancy [15]

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