Abstract
MicroRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. MicroRNAs have been identified in various body fluids under normal conditions and their stability as well as their dysregulation in disease has led to ongoing interest in their diagnostic and prognostic potential. Circulating microRNAs may be valuable predictors of early-life complications such as birth asphyxia or neonatal seizures but there are relatively few data on microRNA content in plasma from healthy babies. Here we performed small RNA-sequencing analysis of plasma processed from umbilical cord blood in a set of healthy newborns. MicroRNA levels in umbilical cord plasma of four male and four female healthy babies, from two different centres were profiled. A total of 1,004 individual microRNAs were identified, which ranged from 426 to 659 per sample, of which 269 microRNAs were common to all eight samples. Many of these microRNAs are highly expressed and consistent with previous studies using other high throughput platforms. While overall microRNA expression did not differ between male and female cord blood plasma, we did detect differentially edited microRNAs in female plasma compared to male. Of note, and consistent with other studies of this type, adenylation and uridylation were the two most prominent forms of editing. Six microRNAs, miR-128-3p, miR-29a-3p, miR-9-5p, miR-218-5p, 204-5p and miR-132-3p were consistently both uridylated and adenylated in female cord blood plasma. These results provide a benchmark for microRNA profiling and biomarker discovery using umbilical cord plasma and can be used as comparative data for future biomarker profiles from complicated births or those with early-life developmental disorders.
Highlights
Complications during childbirth and pre-term births can lead to developmental and neurological dysfunction in later life in a subset of children [1,2,3,4]
They are shuttled between cells via extracellular vesicles [6,7,8] and importantly are abundant in peripheral biofluids including plasma [9], urine [10], cerebrospinal fluid [11], tears, saliva and peritoneal fluid [12]. They were first profiled in human plasma, serum and microvescicles in 2008 [13,14,15] and since subsequent studies have found that their levels in peripheral biofluids often fluctuate in patients with various types of cancer, neurological disorders, sepsis, liver and cardiovascular disease. As such miRNAs have received much interest as potential biomarkers and contain many characteristics which render them ideal biomarker candidates: they are more stable than mRNA as they are resistant to RNase cleavage [19]; expression profiles of miRNAs are often more informative and discriminatory than mRNA profiles; they are abundant and profiling miRNAs is rapid and economical [20]; and their levels often change more rapidly in response to an insult or pathophysiological processes allowing early detection of disease which is critical for progressive illnesses such as cancer, Alzheimer’s disease, epilepsy and early life insults [21,22,23,24,25]
395 miRNAs were detected in three pooled samples from Down syndrome and normal fetal cord blood mononuclear cells (CBMCs) using RNA-seq expression profiling [52]
Summary
Complications during childbirth and pre-term births can lead to developmental and neurological dysfunction in later life in a subset of children [1,2,3,4]. MicroRNAs (miRNAs) are ubiquitously expressed, short non-coding RNAs which finetune gene expression by negatively regulating mRNA translation [5] They are shuttled between cells via extracellular vesicles [6,7,8] and importantly are abundant in peripheral biofluids including plasma [9], urine [10], cerebrospinal fluid [11], tears, saliva and peritoneal fluid [12]. They were first profiled in human plasma, serum and microvescicles in 2008 [13,14,15] and since subsequent studies have found that their levels in peripheral biofluids often fluctuate in patients with various types of cancer, neurological disorders, sepsis, liver and cardiovascular disease (reviewed in [16,17,18]). As such miRNAs have received much interest as potential biomarkers and contain many characteristics which render them ideal biomarker candidates: they are more stable than mRNA as they are resistant to RNase cleavage [19]; expression profiles of miRNAs are often more informative and discriminatory than mRNA profiles; they are abundant and profiling miRNAs is rapid and economical [20]; and their levels often change more rapidly in response to an insult or pathophysiological processes allowing early detection of disease which is critical for progressive illnesses such as cancer, Alzheimer’s disease, epilepsy and early life insults [21,22,23,24,25]
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