Participation of miRNA-23a-3p in Pulmonary Tuberculosis Through Macrophages via the JAK-STAT Pathway

Wenjun Chang,1,* Zheng Li,1,* Qianqian Liang,1 Tao Liu,2 Fengsen Li1 1Department of Respiratory, Unit Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, Xinjiang, People’s Republic of China; 2Department of Xuelian Mountain Campus, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fengsen Li, Department of Respiratory, Unit Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, No. 119, Huang He Road, Urumqi, 830000, People’s Republic of China, Tel +86-13079977217, Email Fengsen602@163.com Tao Liu, Department of Xuelian Mountain Campus, Xinjiang Medical University, 567 Shangde North Road, Shuimogou District, Urumqi, Xinjiang, Uygur Autonomous Region, 830017, People’s Republic of China, Tel +86-13079977217, Email 441318420@qq.comBackground: This study investigated the role of miR-23a-3p in the pathogenesis of tuberculosis (TB)-associated obstructive pulmonary disease (TOPD) and its regulatory impact on THP-1 macrophages via the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway.Methods: Patients with TOPD, TB patients without airflow obstruction (only TB), and healthy controls were recruited. Peripheral blood mononuclear cells were isolated, followed by RNA-seq analysis to identify differentially expressed microRNAs. Gene set enrichment analysis was used to identify enriched biological pathways. Additionally, enzyme-linked immunosorbent assays, Western blot, and flow cytometry were used to explore the miR-23a-3p-mediated modulation in macrophages (such as apoptosis and polarization) via the JAK–STAT pathway.Results: RNA-seq analysis identified miR-23a-3p as being significantly upregulated in TOPD patients. Bioinformatics analysis indicated that miR-23a-3p targets regulation of the JAK–STAT pathway. Overexpression of miR-23a-3p in macrophages led to decreased JAK1 protein expression and reduced levels of phosphorylated JAK1 and STAT1. Functional assays revealed that miR-23a-3p mitigates macrophage apoptosis and macrophage polarization as well as influences inflammatory cytokine production.Conclusion: miR-23a-3p regulates TOPD pathogenesis by modulating macrophage inflammation, apoptosis, and differentiation via the JAK–STAT pathway, making it a promising immunotherapeutic target for future treatments.Keywords: tuberculosis-associated obstructive pulmonary disease, miRNA-23a-3p, JAK–STAT pathway, macrophage