Interactions of Melatonin and MicroRNAs

Abstract

MicroRNAs (miRNAs) are important players in the modulation of cellular functions and contribute substantially to epigenetic changes in the expression of genes. Moreover, the distribution of miRNAs via exosomes and ectosomes opens a vast field of intraorganismal communication, with the potential of spreading pathological deviations, but also curative effects induced by protective agents. Interactions between melatonin and microRNAs are of particular interest, as melatonin is a highly pleiotropic regulator of numerous functions in every organ. The effects of melatonin in correcting pathological alterations in miRNA composition are reviewed, along with the corresponding reversal of cell biological or physiological functions to normal. Additionally, knowledge on the influence of miRNAs on melatonin formation and expression of a melatonin receptor has been considered. The fields in which melatonin has been shown to influence miRNAs are as diverse as metabolic syndrome, liver steatosis, immunology, amyloid toxicity, progenitor cells, and cancer. Readers are encouraged to contribute to systematic studies on melatonin effects on miRNAs using modern RNA sequencing techniques.

Melatonin in macrophage biology: Current understanding and future perspectives

“…Given macrophages have different origins (eg, embryonic origin compared with monocyte derivation) or present in different tissues, such as bone (osteoclasts), lung (alveolar macrophages), and central nervous system (microglial cells), it would be interesting to conduct comparative studies on the influence of melatonin on polarization of macrophage with different origins or tissues. More recently, melatonin was also shown to change the contents of exosomes . These cell‐derived membrane vehicles of 30‐100 nm in diameter carry cargos of miRNAs, miRNA‐sponging lncRNAs (long ncRNAs), and circRNAs (circular RNAs), sometimes DNA, proteins, lipids, and metabolites and mediate intercellular communication by transfer of their contents to recipient cells .…”

“…Melatonin modulates the expression of miRNAs, effects that are meanwhile amply documented and gain increasing attention. Insofar, it is not surprising that melatonin can alter the macrophage polarization status via regulating miRNAs.…”

“…65,181,182 MiR-146 has a robust anti-inflammatory role, and it favors M2 phenotype through targeting TNF receptor-associated factor (TRAF)-6, interleukin-1 receptor-associated kinase (IRAK1), STAT-1, and TLR4. [183][184][185] Melatonin modulates the expression of miRNAs, [186][187][188] effects that are meanwhile amply documented and gain increasing attention. Insofar, it is not surprising that melatonin can alter the macrophage polarization status via regulating miRNAs.…”

“…More recently, melatonin was also shown to change the contents of exosomes. 132,188 These cell-derived membrane vehicles of 30-100 nm in diameter carry cargos of miRNAs, miRNAsponging lncRNAs (long ncRNAs), and circRNAs (circular RNAs), sometimes DNA, proteins, lipids, and metabolites and mediate intercellular communication by transfer of their contents to recipient cells. 268,269 Exosomes can change macrophage phenotypes; hence, it will be interesting to study whether exosomes (especially exosomal cargos such as miRNAs, lncRNAs and metabolites) are associated with melatonin-mediated macrophage polarization.…”

Extended Signaling by Melatonin

“…As exosomes and ectosomes are found in all body fluids, they transmit regulatory messages over long distances to target cells. By virtue of this property, they are discussed in terms of spreading dysregulatory information of pathologies, but may also spread protective, correcting information upon curative treatment [109].…”