Evidence and potential in vivo functions for biofluid miRNAs: From expression profiling to functional testing

“…It has been demonstrated that miRNAs may act synergistically in gene expression regulation (Kilikevicius et al, 2021), that, in the case of ticks, can lead to a cooperative effect in host homeostasis modification. This synergy can enhance repression strength, allowing therefore that even a limited number of miRNAs exert a significant influence on their target mRNAs, which may be particularly relevant for I. ricinus , where delivery to host cells may be quantitatively limited (Chevillet et al, 2014; Iftikhar & Carney, 2016; Turchinovich et al, 2016). Therefore, we examined the potential cooperative effects of the complete set of I. ricinus miRNAs, focusing on their ability to target conserved neighboring sites within the same host mRNA.…”

“…The question whether miRNAs from body fluids play biological functions is still debated 44,45 ; it has been calculated that miRNAs expressed below ~100 copies per cell have little regulatory capacity 99 and that the concentration of extracellular miRNAs may be too low to exert in vivo effect 100 . However, there are several indications that exosomal miRNAs can be transferred in vitro to recipient cells where they can affect gene expression 44,101 and the majority of miRNAs from human saliva was shown to be concentrated in exosomes 102 . Moreover, circulating exosomal miRNAs from adipose tissue have been recently shown to regulate gene expression in the liver 46 , reinvigorating the hypothesis of an in vivo functional role of exosomal miRNAs.…”

“…Extracellular circulating miRNAs have been detected in serum, so they might be biomarkers of diseases103031. Most studies have proposed that extracellular miRNAs can be packaged into membrane-associated organelles such as exosomes, microvesicles, and extracellular vesicles1032, but the mechanisms and origins of vesicle-free extracellular miRNAs remain unclear.…”

“…Most studies have proposed that extracellular miRNAs can be packaged into membrane-associated organelles such as exosomes, microvesicles, and extracellular vesicles1032, but the mechanisms and origins of vesicle-free extracellular miRNAs remain unclear. To our knowledge, our data are the first to identify miRNA exocytosis by LDCV fusion.…”