Differential Expression of miRNAs in Tuberculosis

Molecular studies regarding regulatory elements such as small non-coding RNAs and their mechanisms are poorly understood in infectious diseases. Tuberculosis is one of the oldest infectious diseases of humanity, and it is still a challenge to prevent and treat it. The control of the infection as well as its diagnosis are still complex, and treatments used are linked to several side effects.Thus, this study aimed to investigate the miRNA's expression profile in order to identify possible biomarkers of this disease. We applied next generation sequencing to investigate the global expression profile of miRNAS from blood samples of infected patients with tuberculosis, their respective hospital controls and external controls. 22 collected samples (9 patients, 6 hospital controls and 7 external controls) were prepared to be explored and passed a quality control pipeline (Trimmomatic software) and an alignment (STAR software) and read's count (HTSeq software) processes to perform differential expression (edgeR package), target genes (miRTarbase database), gene set enrichment (DAVID and Reactome databases) and miRNA-gene network analysis. A total of 174 altered miRNAs were observed in all analysis performed, among which, only three differentially expressed miRNAs (hsa-let-7g-5p, hsa-miR-486-3p and hsa-miR-4732-5p), which are suggested to participate in important granuloma regulation and formation pathways involved in the three phenotypic types of granuloma immune physiopathology, were found between the investigated patients and their respective hospital controls. These results suggested that miRNAs may be involved in immune modulation through the formation and maturation of granulomas, regulating the repertoire of genes expressed in cells of the immune system. These findings encourage the application of miRNAs as potential biomarkers.