miRNA Differential Expression Profile Analysis and Identification of Potential Key Genes in Active Tuberculosis

Background: Tuberculosis (TB), caused by Mycobacterium TB (MTB), remains a significant global health issue, particularly in developing nations. MicroRNAs (miRNAs) are non-coding RNAs (ncRNAs) that modulate immune responses and play a pivotal role in the pathogenesis of MTB by altering host immune defenses. Insights into the regulatory functions of these miRNAs have revealed mechanisms through which MTB evades immune surveillance and establishes persistent infections, highlighting the critical role of miRNA networks in TB pathogenesis. Objective: The purpose of this study was to analyze miRNA expression in plasma from TB patients, to predict target genes, and to construct regulatory networks to elucidate the roles of miRNAs in TB pathogenesis. Methods: This study recruited six participants, comprising three patients with active TB and three healthy controls (HCs). High-throughput sequencing was employed to profile miRNAs. Differentially expressed miRNAs (DEMs) were identified, and their target genes were predicted using the TargetScan and miRWalk databases. The Gene Ontology (GO) and KEGG databases facilitated the construction of regulatory pathway networks. Additionally, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyzed protein-protein interaction (PPI) networks for genes enriched in immune-related pathways, highlighting key genes. Results: The study identified 23 DEMs, with 17 upregulated and 6 downregulated. PRKCB was recognized as a potential diagnostic target. Analyses using GO and KEGG identified pivotal pathways implicated in TB pathogenesis, particularly involving miRNAs hsa-let-7a-5p and NovelmiRNA-41 in the PRKCB-related regulatory network. Conclusion: We identified 23 DEMs and a key gene, PRKCB, associated with TB pathogenesis. The MAPK and chemokine pathways were identified as central to the regulatory mechanisms of MTB infection, presenting new possibilities for the development of early diagnostic and therapeutic strategies. Overall design: miRNA-seq profiling of human serum that were collect from 3 patients with active tuberculosis and 3 healthy control.