Integrated co-expression analysis of regulatory elements (miRNA, lncRNA, and TFs) in bovine monocytes induced by Str. uberis.

Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), together with transcription factors, are critical pre-, co-, and post-transcriptional regulators. In addition to their criteria as ideal biomarkers, they have great potential in disease prognosis, diagnosis, and treatment of complex diseases. Investigation of regulatory mechanisms in the context of bovine mastitis, as most common and economic disease in the dairy industry, to identify elements influencing the expression of candidate genes as key regulators of the mammary immune response is not yet fully understood. Transcriptome profiles (50 RNA-Seq and 50 miRNA-Seq samples) of bovine monocytes induced by Str. uberis were used for co-expression module detection and preservation analysis using the weighted gene co-expression network analysis (WGCNA) approach. Assigned mi-, lnc-, and m-modules used to construct the integrated regulatory networks and miRNA-lncRNA-mRNA regulatory sub-networks. Remarkably, we have identified 18 miRNAs, five lncRNAs, and seven TFs as key regulators of str. uberis-induced mastitis. Most of the genes introduced here, mainly involved in immune response, inflammation, and apoptosis, were new to mastitis. These findings may help to further elucidate the underlying mechanisms of bovine mastitis, and the discovered genes may serve as signatures for early diagnosis and treatment of the disease.