Extracellular vesicles (EVs) are nanoscopic structures released by all cell types, playing a crucial role in cellular communication. EVs contain various types of RNAs, and a significant number of studies in the field of biomarker research have focused on the RNA content of these vesicles, particularly microRNAs. Saliva is an easily and non-invasive obtainable body fluid that is being increasingly studied for the identification of biomarkers associated with oral and systemic disorders. Early studies investigating salivary RNA distribution reported that the majority of its microRNA content seemed to be associated with EVs. Recently, an RNAseq analysis of host and microbial salivary RNA content in different salivary fractions reported that a majority of the most abundant microRNAs (miRNAs) were detected in both EV-enriched and unenriched saliva fractions. In this letter we raise the hypothesis that this high correlation regarding the miRNA content among saliva fractions might be partially explained by the presence of alternative, overlooked sources of miRNAs in saliva such as lipoproteins. The focus of this report is to raise awareness regarding potential contaminants in EV saliva preparations and to emphasize the need of further research aimed at directly assessing the contribution of these alternative miRNA carriers.
extracellular vesicles; saliva; lipoproteins; miRNAs; biomarker research; cancer; exosomes