Abstract
Epigenetic mechanisms have emerged as an important pathway through which environmental exposures can affect health through the regulation of gene expression without changes in DNA sequence: microRNAs (miRNAs) are short non-coding RNAs that target protein-coding mRNAs, leading to post-transcriptional repression. They are involved in important physiologic processes, but little is known about how miRNA expression may change with age in children. We used an nCounter miRNA assay to assess the expression of 43 miRNAs in buffy coat samples collected from newborns (n = 121) and 7-year-old (n = 142) children. We identified 36 miRNAs that were differentially expressed between newborns and 7-year-olds after controlling for blood cell composition. Using pathway analysis, we found that differentially expressed miRNAs targeted genes enriched for processes related to post-translational modifications, metabolism, and immune response. Our study found that unlike adults, where miRNA expression levels in peripheral blood may decrease with age, expression levels of most miRNAs increased from birth to mid-childhood. This may be reflective of the role miRNAs may play in the highly coordinated mechanisms regulating genes involved in children’s development. Furthermore, it will be important to adjust for both age and blood cell composition in future pediatric studies of miRNA expression in blood.
Highlights
Epigenetics has emerged as an important biological mechanism through which environmental exposures can affect health [1,2,3]
Among the 43 miRNAs assessed, we found cord blood (Table indicating that white blood cell proportions may influence expression of in miRNAs that had suggestive associations (2 positive and 6 negative), with blood cell proportions some miRNAs
We found 14 miRNAs that were lower in girls compared to boys at both ages and 3 miRNAs and miR-301-3p) that were lower in girls compared to boys at both ages and 3 miRNAs
Summary
Epigenetics has emerged as an important biological mechanism through which environmental exposures can affect health [1,2,3] Epigenetic marks such as DNA methylation, non-coding RNA, and histone modifications regulate gene expression without changes in DNA sequence. Growing evidence has demonstrated that non-coding RNAs play a major role in important cellular processes and disease etiology [8]: miRNAs are short non-coding RNAs of about 18–22 nucleotides in length. They bind to specific mRNA sequences via miRNA binding sites, thereby blocking translation. MiRNAs have been associated with health outcomes such as fetal growth [11], cancer [12], and cardiovascular disease [13]
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