An innovative approach to predict immune-associated genes mutually targeted by cow and human milk microRNAs expression profiles.

Aim: Milk is rich in miRNAs - the endogenous small non-coding RNA responsible for gene post-transcriptional silencing. Milk miRNAs were previously evidenced to affect consumer's immune response. While most studies relied on a few well-characterized milk miRNAs to relate their immunoregulatory roles on target genes among mammals, this study introduced a procedure to predict the target genes based on overall milk miRNA expression profiles - the miRNome data of cow and human.

Materials And Methods: Cow and human milk miRNome expression datasets of cow and human milk lipids at 2, 4, and 6 months of lactation periods were preprocessed and predicted for their target genes using TargetScanHuman. Enrichment analysis was performed using target genes to extract the immune-associated gene ontology (GO) terms shared between the two species. The genes within these terms with more than 50 different miRNAs of each species targeting were selected and reviewed for their immunological functions.

Results: A total of 146 and 129 miRNAs were identified in cow and human milk with several miRNAs reproduced from other previous reports. Enrichment analysis revealed nine immune-related GO terms shared between cow and human (adjusted p≤0.01). There were 14 genes related to these terms with more than 50 miRNA genes of each species targeting them. These genes were evidenced for their major roles in lymphocyte stimulation and differentiation.

Conclusion: A novel procedure to determine mutual immune-associated genes targeted by milk miRNAs was demonstrated using cow and human milk miRNome data. As far as we know, this was the 1st time that milk miRNA target genes had been identified based on such cross-species approach. Hopefully, the introduced strategy should hereby facilitate a variety of cross-species miRNA studies in the future.