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How miRNAs influence health and disease

  • Jan 5, 2024
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How miRNAs influence health and disease

In a recent study published in Nutrients, researchers reviewed the role of dietary microRNAs (miRNAs) in health and disease.

Study: Dietary Epigenetic Modulators: Unravelling the Still-Controversial Benefits of miRNAs in Nutrition and Disease. Image Credit: ART-ur/Shutterstock.com

Background

Diet is one of the lifestyle factors with a substantial impact on health. Unhealthy diets have been responsible for several chronic degenerative diseases, such as cardiovascular disease, obesity, cancer, and diabetes.

Food intake may impact gene expression and disease susceptibility by regulating epigenetic modulators. miRNAs are critical in biological processes and gene regulation.

miRNAs have been detected in blood, plasma, serum, saliva, breast milk, and urine, and changes in their levels are associated with various chronic syndromes.

Thus, preserving the miRNA profile could help prevent diseases and maintain good health. Moreover, miRNAs have been reported in plants and animals as well. Plant miRNAs bind to recipient targets with perfect complementarity and function as small interfering RNAs.

By contrast, animal-derived miRNAs bind to host mRNA targets with an imperfect complementarity and induce their translational repression. A single exogenous miRNA (xenomiRNA) can recognize and modulate multiple target genes in the host due to imperfect complementarity.

Nevertheless, the clinical relevance of xenomiRNAs from foods in human disease is unclear. In the present study, researchers reviewed the role of dietary miRNAs in health and disease.

Dietary xenomiRNAs

RNA sequencing analyses have identified various miRNAs in the edible portions of chicken eggs. A recent study reported the presence of miRNA-related exosomes from chicken eggs in humans and mice.

These miRNA exosomes accumulated in the intestine, lung, and brain in C57BL/6 mice and regulated memory function and spatial learning.

Another study evaluated the effects of chronic administration of pork-derived exosomes in a mouse model. The study noted that increased plasma levels of miR-1, miR-206, miR-99a, and miR-133a-3p impaired glucose and insulin metabolism and caused lipid droplet accrual in the liver.

Besides, 678 miRNAs have been reported in bovine milk-derived exosomes that are involved in multiple cellular metabolic pathways.

MiR-148a is the most abundant miRNA in milk exosomes and can modulate oral cavity homeostasis. It can also inhibit phosphatase and tensin homolog (PTEN) and 5’ AMP-activated protein kinase (AMPK), which are inhibitors of the mammalian target of rapamycin complex 1 (mTORC1), a critical regulator involved in multiple metabolic pathways.

miR-156a, present in cabbage, lettuce, and spinach, can target junctional adhesion molecule (JAM)-A and suppress atherosclerosis development in aortic endothelial cells.

Furthermore, miR-159, abundant in broccoli, has been shown to suppress breast tumor development in in vitro and in vivo models.

An analysis of miRNAs from rice revealed their binding affinity for various human genes involved in neurological diseases, cancer, and cardiovascular disease.

Studies have reported that miR168 circulating levels in mice/human serum after rice consumption were associated with decreased clearance of low-density lipoprotein.

Moreover, hvu-miR-168-3p derived from rice aleurone reduced blood glucose levels and increased the expression of glucose transporter 1 (GLUT1). Exosome-like nanoparticles from 11 fruits harbor miRNAs capable of targeting genes that encode inflammatory mediators.

Food nutrients as regulators of miRNAs in disease

Nutrients in foods impact the miRNA profile by directly or indirectly modulating gene expression. Fatty acids, vitamins, phytochemicals, and vitamins have been reported to regulate miRNA levels.

For instance, resveratrol exerts anti-inflammatory actions by upregulating miR-Let7a and miR-663 and reducing miR-155 in monocytes stressed with lipopolysaccharide (LPS).

Besides, resveratrol has been reported to ameliorate liver fibrosis and reduce apoptosis of hepatocytes by inhibiting miR-190a-5p. Further, curcumin treatment of macrophages has been shown to decrease miR-155 levels to counteract LPS-induced inflammation.

In Alzheimer’s disease, quercetin exhibited a neuroprotective role through miRNA homeostasis in neuronal cells by preventing the altered expression of miR-125b, miR-2218, and miR-26a.

Furthermore, treating a rat model of Alzheimer’s disease with resveratrol and selenium nanoparticles decreased neuroinflammation and metabolic dysfunction by upregulating sirtuin 1 and amyloid-β clearance and downregulating miR-143, interleukin (IL)-1β, and signal transducer and activator of transcription 3 (STAT3).

Besides, one study reported that resveratrol attenuated colitis-induced tumorigenesis by upregulating miR-455 and miR-101b.

In lung cancer cells, curcumin treatment inhibited cell invasion by upregulating miR-98, which suppresses matrix metalloproteinase 2 (MMP2) and MMP9 pathways.

Further, quercetin exhibited anti-cancer properties by enhancing apoptosis in non-small cell lung carcinoma (NSCLC) cells through an increase in miR-34a-5p and the downregulation of the small nucleolar RNA host gene 7 (SNHG7).

Concluding remarks

A growing body of evidence highlights the potential of dietary miRNAs in modulating human pathophysiology, opening avenues for new diet-based interventions.

Nevertheless, preventive strategies based on xenomiRNAs have limitations, including poor biostability and bioavailability, unknown complications associated with high intake, and multiple targets. Therefore, future studies are necessary to expand the knowledge base.


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