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

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.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4646-5) contains supplementary material, which is available to authorized users.

Association of plasma microRNA expression with age, genetic background and functional traits in dairy cattle

“…Subsequent analyses were focused on the 12 validated age-related miRNAs. According to our previous data 23 , nearly all of these miRNAs are expressed at higher levels in plasma samples than blood cells. Changes in circulating levels of some of the miRNAs were consistent with previous studies in other species, including miR-126-5p 25 , 26 , miR-127 16 , 27 , miR-154c 27 and miR-29 family miRNAs 7 .…”

“…1b ) correspond to miRNAs that are enriched in blood cells (miR-451, 16a, 16b, 486) 23 . However, several miRNAs which according to our previous study 23 are primarily expressed in plasma compared to blood cells, were also present (miR-195, 27a-3p, 22-3p, 30a-5p).

Figure 1 Plasma miRNA abundance.

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“…In addition, our approach would not allow the discovery of novel miRNAs, since the list of miRNAs to be measured was pre-defined. However, our existing miRNA data from previous studies 15 , 23 , 56 ensured the majority of the detectable miRNAs in bovine plasma, which might provide insights into function or be used as biomarkers, were profiled in this study.…”

Plasma extracellular vesicle miRNAs as potential biomarkers of superstimulatory response in cattle

“…This has been commonly observed in the exosomal and extracellular studies compared to cellular RNAseq. For instance, small RNAseq analysis from bovine plasma and blood cells exhibited mapping rates of 38.1% and 94.3%, respectively 40 . Moreover, comparing cellular and exosomal RNA biotypes revealed that exosomes contained a greater proportion of Piwi-interacting RNA (piRNA) and ribosomal RNA, while cells expressed proportionally more miRNA and small nucleolar RNA 41 .…”

Fecal microRNAs as Innovative Biomarkers of Intestinal Diseases and Effective Players in Host-Microbiome Interactions

“…An interesting class of miRNAs includes "circulating miRNAs" characterized by their active release through EVs or passive release upon cell death [12,30,[65][66][67][68][69]. Several studies have shown that miRNAs can be identified in a variety of body fluids, including plasma, saliva, urine, seminal fluids, breast milk, cerebrospinal fluid and more recently also in feces, leading to the definition of circulating miRNAs [70][71][72][73][74].…”