Detection of long non-coding RNAs in human breastmilk extracellular vesicles: Implications for early child development

Abstract

Breastmilk has many documented beneficial effects on the developing human infant, but the components of breastmilk that influence these developmental pathways have not been fully elucidated. Increasing evidence suggests that non-coding RNAs encapsulated in extracellular vesicles (EVs) represent an important mechanism of communication between the mother and child. Long non-coding RNAs (lncRNAs) are of particular interest given their key role in gene expression and development. However, it is not known whether breastmilk EVs contain lncRNAs. We used qRT-PCR to determine whether EVs isolated from human breastmilk contain lncRNAs previously reported to be important for developmental processes. We detected 55 of the 87 screened lncRNAs in EVs from the 30 analyzed breastmilk samples, and CRNDE, DANCR GAS5, SRA1 and ZFAS1 were detected in >90% of the samples. GAS5, SNHG8 and ZFAS1 levels were highly correlated (Spearman's rho>0.9; P<0.0001), which may indicate that the loading of these lncRNAs into breastmilk EVs is regulated by the same pathways. The detected lncRNAs are important epigenetic regulators involved in processes such as immune cell regulation and metabolism. They may target a repertoire of recipient cells in offspring and could be essential for child development and health. Further experimental and epidemiological studies are warranted to determine the impact of breastmilk EV-encapsulated lnRNAs in mother to child signaling.

Potential of long non‐coding RNAs in cancer patients: From biomarkers to therapeutic targets

“…Third , lncRNAs have been identified from serum, plasma, saliva and urine. A recent study reported lncRNAs dysregulation in the extracellular vesicles of human breast milk suggesting their potential in child health and development. Whether lncRNAs from breast milk possess clinical significance for cancer patients remain to be explored.…”

Roles of MicroRNA across Prenatal and Postnatal Periods

“…During the following 20 years, researchers around the world working in different fields, continued to investigate RNA control of gene expression [33] and its role in cell-to-cell signaling [34]. Today we are aware that extracellular noncoding RNA, such as miRNA and long non-coding RNA (lncRNA) [35,36], are involved in cellular communication, may be involved in childhood development, and are protected from RNases through association with RNA-binding proteins and/or by their encapsulation inside extracellular vesicles [36,37,38]. …”

“…They can mediate the transfer of proteins, lipids, and nucleic acids, including miRNAs and lncRNAs [36], and have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes [39]. EV have biological functions linked to sperm maturation and motility, follicular growth, oocyte meiosis, steroidogenesis, and the prevention of polyspermy after fertilization.…”

Association between breastfeeding and DNA methylation over the life course: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC)

“…This may be due to analysing a surrogate tissue, limited statistical power to detect more CpGs, and limited knowledge about the health effects of the methylation sites that were detected. Moreover, the effects of breastfeeding on health and development may be mediated through other epigenetic processes, such as non-coding RNAs [35, 36], as well as a host of mechanisms other than epigenetics, including provision of nutrients (e.g., pre-formed long-chain polyunsaturated fatty acids, which is a plausible mediator of the benefits on IQ [37]), antibodies and other immunoactive compounds, antimicrobials, and important effects on the gut microbiome [1].…”