Exosomal ncRNAs profiling of mycobacterial infection identified miRNA-185-5p as a novel biomarker for tuberculosis

Abstract Background: There are ever increasing researches implying that noncoded RNAs (ncRNAs) specifically circular RNAs (circRNAs) and microRNAs (miRNAs) in exosomes play vital roles in respiratory disease. However, the detailed mechanisms persist to be unclear in mycobacterial infection. Methods: In order to detect circRNAs and miRNAs expression pattern and potential biological function in tuberculosis, we performed immense parallel sequencing for exosomal ncRNAs from THP-1-derived macrophages infected by Mycobacterium tuberculosis H37Ra, Mycobacterium bovis BCG and control Streptococcus pneumonia, respectively and uninfected normal cells. Besides, THP-1-derived macrophages were used to verify the validation of differential miRNAs, and monocytes from PBMCs and clinical plasma samples were used to further validate differentially expressed miR-185-5p. Results: Many exosomal circRNAs and miRNAs associated with tuberculosis infection were recognized. Extensive enrichment analyses were performed to illustrate the major effects of altered ncRNAs expression. Moreover, the miRNA–mRNA and circRNA–miRNA networks were created and expected to reveal their interrelationship. Further, significant differentially expressed miRNAs based on Exo-BCG, Exo-Ra and Exo-Control, were evaluated, and the potential target mRNAs and function were analyzed. Eventually, miR-185-5p was collected as a promising potential biomarker for tuberculosis. Conclusion: Our findings provide a new vision for exploring biological functions of ncRNAs in mycobacterial infection and screening novel potential biomarkers. To sum up, exosomal ncRNAs might represent useful functional biomarkers in tuberculosis pathogenesis and diagnosis.