The Molecular Dialogue: Cow’s Milk and Its Effect on Human Gene Expression Patterns

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Understanding the Impact of Cow’s Milk on Human Genes

Imagine you are sipping on a glass of milk. Have you ever wondered if this milk could do more than just provide you with calcium and vitamins? Scientists have been exploring how tiny molecules in cow’s milk might affect our bodies in ways we never imagined. This chapter will break down the fascinating study of how molecules from cow’s milk might influence human genes, using simple language that anyone can understand.

What are miRNAs?

miRNAs, or microRNAs, are tiny molecules found in many living things, including humans and cows. Think of them as tiny messengers that help control how our genes work. Genes are like instructions for building and running our bodies, and miRNAs help make sure these instructions are followed correctly. They are very small, only about 18-24 building blocks long, but they play a big role in keeping our bodies functioning properly.

miRNAs in Milk

Both human and cow’s milk contain miRNAs. These miRNAs are often packaged in tiny bubbles called exosomes, which protect them and help them travel through the body. When you drink milk, these exosomes help the miRNAs survive the trip through your stomach and intestines, allowing them to get into your bloodstream.

Can Cow’s Milk miRNAs Affect Humans?

Scientists have discovered that the miRNAs in cow’s milk can enter the human bloodstream and may influence how our genes work. This means that the tiny molecules from cow’s milk could potentially help regulate certain functions in our bodies.

For example, one specific miRNA found in cow’s milk, called bta-miR-574-5p, has been shown to interact with many human genes. This miRNA is the same in both cows and humans, indicating that it plays a crucial role in both species. Researchers believe that bta-miR-574-5p can help control the activity of many genes, which might affect various bodily processes and development.

The Big Discovery

In the study, scientists looked at 245 different miRNAs found in cow’s milk and found that 103 of them could potentially affect human genes. Some miRNAs were found to target many genes at once. For instance, bta-miR-151-5p and bta-miR-151-3p each target 11 human genes. This means these miRNAs might have a big influence on how certain genes behave in our bodies.

Why is This Important?

Understanding how miRNAs from cow’s milk can affect human genes is important for several reasons:

  • Nutrition: Knowing which miRNAs are in cow’s milk and how they affect us can help improve our diets, especially for babies who rely on milk for nutrition.
  • Health: miRNAs might play a role in preventing or treating certain diseases. By studying how they work, we could develop new ways to use milk to help keep us healthy.
  • Cross-Species Benefits: Since miRNAs are similar in cows and humans, this research shows how molecules from one species can help regulate the biology of another, revealing the interconnectedness of living organisms.

Simplified Example

Imagine you have a recipe book (your genes) that tells you how to bake a cake (your body’s functions). The miRNAs are like little helpers that make sure you follow the recipe correctly. Sometimes, these helpers come from the milk you drink. If they see you adding too much sugar, they might remind you to stop, ensuring your cake turns out just right. Similarly, miRNAs from cow’s milk can help make sure your body’s “recipes” are followed properly, keeping you healthy.

Scientists are excited to continue exploring how miRNAs from cow’s milk can affect human health. They plan to conduct more experiments to confirm their findings and understand exactly how these tiny molecules work in our bodies. This research could lead to new ways to use milk and other foods to improve our health and well-being.

In simple terms, the study of miRNAs from cow’s milk reveals that these tiny molecules can travel through our bodies and potentially help regulate our genes. This discovery opens up new possibilities for nutrition and health, showing that milk does more than just provide us with basic nutrients—it might also play a role in keeping our genes in check and our bodies functioning smoothly. So, the next time you drink a glass of milk, remember that you’re not just getting calcium, but also tiny helpers that might be looking out for your health.

The deep study….

MicroRNAs (miRNAs) are 18–24-nucleotide-long RNA molecules that play a critical role in regulating post-transcriptional gene expression. These nanoscale entities are highly conserved across species and exert their regulatory effects by either inhibiting mRNA translation or degrading mRNA through exonuclease action (Huntzinger & Izaurralde, 2011; Fabian & Sonenberg, 2012; Ipsaro & Joshua-Tor, 2015; Jonas & Izaurralde, 2015). Recent research has illuminated the presence and potential functional roles of miRNAs in various biological fluids, including milk from both humans and cows (Chen et al., 2010; Weber et al., 2010).

The enrichment of miRNAs in milk, particularly within extracellular vesicles such as exosomes, underscores their stability and functional potential. These vesicles, ranging from 30–120 nm in diameter, are derived from various cell types and are present in all biological fluids, including blood plasma, serum, urine, breast milk, and colostrum (Kosaka et al., 2010; Gu et al., 2012; Xiao et al., 2018; Yun et al., 2021; Zeng et al., 2020; Zeng et al., 2021). The intriguing possibility that miRNAs from food sources can withstand the digestive process and influence gene expression in the consumer has been suggested by Zhang et al. (2012). Specifically, their research indicated that plant-derived exogenous miRNAs (ex-miRs) could enter the bloodstream and regulate gene expression.

In the context of mammalian predators, exogenous miRNAs are ingested with raw food, and this pathway of miRNA transmission has been preserved through evolution. This article aims to explore the interaction of bovine miRNAs (bta-miRNAs) from cow’s milk with human gene expression. Given the conserved nature of miRNAs across species, understanding these interactions could reveal significant insights into gene regulation and potential therapeutic applications.

The Interaction of Milk bta-miRNAs with mRNAs of Human Genes

Overview of bta-miRNAs in Cow’s Milk

Cow’s milk has been shown to contain numerous miRNAs, many of which are packaged within exosomes, providing stability and facilitating their absorption through the gastrointestinal tract (Aarts et al., 2021; Diomaiuto et al., 2021; Gao et al., 2021; Marsh et al., 2021; Wehbe & Kreydiyyeh, 2021). Research by Izumi et al. (2012) demonstrated that colostrum contains higher levels of miRNAs compared to mature milk, particularly those related to immune and developmental functions. These miRNAs are resistant to acidic conditions and RNases, suggesting their potential to remain functional even after industrial processing.

Human studies have confirmed the absorption of biologically meaningful amounts of miRNAs from cow’s milk, which enter peripheral blood mononuclear cells and potentially other peripheral tissues, thereby influencing human gene expression (Baier et al., 2014; Lukasik & Zielenkiewicz, 2014; Shu et al., 2015; Yim et al., 2016). These findings pave the way for exploring how bta-miRNAs from cow’s milk can impact human physiology and gene networks.

Specific bta-miRNAs and Their Human Gene Targets

Supplementary Table S1 presents data on the potential influence of various milk bta-miRNAs on human protein synthesis. Out of 245 identified milk bta-miRNAs (Chen et al., 2010), 103 miRNAs were found to have the capability to affect human gene expression. Some miRNAs, such as bta-miR-151-5p and bta-miR-151-3p, which originate from the same pre-miRNA, each target 11 genes. This suggests an optimized energy expenditure in miRNA synthesis and a shared dependency of target genes on a single source.

Several bta-miRNAs exhibit a broad range of target genes, with bta-miRNA-320, bta-miRNA-345-5p, bta-miRNA-614, bta-miRNA-1296b, and bta-miRNA-149 having 11, 12, 14, 15, and 26 target genes, respectively. These miRNAs likely have a significant impact on human gene expression due to the large number of targets.

Case Study: bta-miR-574-5p

A particularly noteworthy miRNA is bta-miR-574-5p, identified in cow’s milk, which has between one to 14 binding sites (BSs) in the mRNAs of 209 human genes (Supplementary Table S2). Both bta-miR-574-5p and human miR-574-5p share identical nucleotide sequences, indicating crucial roles in fetal development and the regulation of numerous genes in both cow and human genomes. The high free energy values (∆G from −115 kJ/mol to −123 kJ/mol) indicate strong interactions between miRNAs and their binding sites.

Among the human genes targeted by bta-miR-574-5p, 28 genes have clusters of 14 or more binding sites, highlighting the extensive regulatory potential of this miRNA. These genes also have binding sites for miR-574-5p in bovine species, further suggesting a conserved regulatory function across species.

High Complementarity of Bta-miRNAs and mRNAs of Human Genes

The total number of human target genes for bta-miRNAs with 98–100% complementarity is 32 (Table 2). Among these, bta-miR-2881, bta-miR-2444, bta-miR-11975, bta-miR-135a, bta-miR-151-5p, bta-miR-1777b, bta-miR-1777a, bta-miR-2478, bta-miR-136, bta-miR-432, bta-miR-127, bta-miR-433, bta-miR-431, bta-miR-1282, and bta-miR-11976 show full complementarity to 13 human gene mRNAs. Eight of these human miRNAs have identical names and nucleotide sequences as their bovine counterparts, and their target genes have been experimentally verified (Davis et al., 2005; Wang J. et al., 2016; Yurikova et al., 2019).

The high degree of sequence conservation between bta-miRNAs and human miRNAs suggests a potential for cross-species regulatory functions. For example, bta-miR-2444 targets five human genes (CXorf38, PTP4A2, ATP2B2, CELF2, and HDX), and bta-miR-1777b targets three (MEX3A, RHOB, and HCN2). These miRNAs exhibit a strong potential for regulating human gene expression due to their high complementarity and significant free energy of interaction values (ranging from −93 to −127 kJ/mol).

Interaction Characteristics and Functional Implications

Figure 1 illustrates the hydrogen bond construction between all nucleotides of bta-miR-1584-5p, bta-miR-2444, and bta-miR-196a with their binding sites in human mRNAs. The MirTarget program considers non-canonical pairs A-C and G-U, preserving the spiral structures of both miRNA and mRNA, which stabilizes the duplex through stacking interactions (Garg & Heinemann, 2018).

The interactions of bta-miR-11975, bta-miR-11976, and bta-miR-2885 with the coding sequences (CDS) of human mRNAs were also analyzed. These miRNAs target 118 human genes, with binding site clusters located in CDSs. The binding sites often consist of repeating GCC triplets encoding oligopeptides, indicating a potential mechanism for miRNA-mediated regulation of protein synthesis.

miRNAs and Human Diseases

Supplementary Table S11 lists genes targeted by bta-miRNAs that are associated with various human diseases, including cancers, neurodegenerative disorders, and cardiac diseases. For instance, bta-miR-151-5p and bta-miR-151-3p have binding sites in genes associated with breast cancer, while bta-miR-11976 targets genes related to myeloid leukemia and gastric cancer.

The potential for bta-miRNAs to influence oncogenes or onco-suppressors highlights their dual role in oncogenesis. For example, increased miR-222 expression suppresses a breast cancer tumor suppressor, whereas decreased miR-222 levels elevate the expression of the tumor suppressor (Said et al., 2021). Conversely, miR-345-5p acts as a tumor suppressor in lung adenocarcinoma cells by inhibiting oncogene expression (Zhou Y. et al., 2021).

Discussion

This study utilized bioinformatics analyses to predict the interaction networks between bovine miRNAs and human mRNAs. The high transportability and sequence conservation of certain miRNAs suggest significant regulatory potential across species. Identical sequences between bovine and human miRNAs indicate a higher probability of cross-species gene regulation.

Human breast milk and cow’s milk share a substantial overlap in miRNA expression profiles, with 95% of miRNAs expressed in human milk also present in cow milk (Chen et al., 2010). This suggests that miRNAs in cow’s milk can be transferred to humans, potentially regulating gene expression in various tissues.

Future Directions

Future research should focus on experimental validation of these bioinformatics predictions. Specifically, it is essential to determine the pathways through

which milk-derived exosomal miRNAs are transported and their subsequent effects on human gene expression. Understanding these mechanisms could pave the way for using exogenous miRNAs as biocompatible regulators of biological processes and potential therapeutic agents.

Furthermore, investigating the role of miRNAs in various diseases, particularly their dual roles in oncogenesis and tumor suppression, could provide valuable insights into novel treatment strategies. The identification of specific miRNAs that target multiple human genes associated with diseases underscores their potential as therapeutic targets.

Conclusion

The study of bovine miRNAs and their potential to affect human gene expression is a burgeoning field with significant implications for understanding cross-species gene regulation. The identification of miRNAs in cow’s milk that can target human genes opens new avenues for research into the therapeutic applications of exogenous miRNAs. As bioinformatics predictions are experimentally validated, the potential for using miRNAs as regulators of gene expression and therapeutic agents will become increasingly evident.


reference link : https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.705350/full


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