Up-regulation of circRNA-0003528 promotes mycobacterium tuberculosis associated macrophage polarization via down-regulating miR-224-5p, miR-324-5p and miR-488-5p and up-regulating CTLA4

• Published in: Aging (Albany, NY.) Vol. 12; no. 24; pp. 25658 - 25672
• Main Authors: Huang, Zikun, Yao, Fangyi, Liu, Jun, Xu, Jianqing, Guo, Yang, Su, Rigu, Luo, Qing, Li, Junming
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 09.12.2020
• Subjects: Case-Control Studies; Cell Differentiation; CTLA-4 Antigen - genetics; CTLA-4 Antigen - immunology; CTLA-4 Antigen - metabolism; Down-Regulation; Humans; Macrophages - immunology; Macrophages - metabolism; Macrophages, Alveolar - immunology; Macrophages, Alveolar - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Phenotype; Research Paper; RNA, Circular - genetics; RNA, Messenger - metabolism; THP-1 Cells; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - immunology; U937 Cells; Up-Regulation; miR-224-5p; CTLA4; macrophage polarization; circRNA-0003528; tuberculosis
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.104175

In this study, we selected several candidate miRNAs to study their possible relationships with tuberculosis. The expression of hsa_circ_0003528 was negatively correlated with the expression of miR-224-5p, miR-324-5p, miR-488-5p, miR-587, and miR-668, while the expression of hsa_circ_0003528 was positively correlated with the expression of miR-224-5p, miR-324-5p and miR-488-5p. No evident difference was observed between tuberculosis and healthy control groups in terms of the expression of miR-587 and miR-668. The findings of this study demonstrated that miR-224-5p, miR-324-5p and miR-488-5p were all ceRNAs of circRNA-0003528 by sponging each other and CTLA4 was found to be a shared target gene of miR-224-5p, miR-324-5p and miR-488-5p. Furthermore, we found that up-regulation of circRNA-0003528 promoted tuberculosis associated macrophage polarization by promoting expression CTLA4, which was mediated by the down-regulation of miR-224-5p, miR-324-5p and miR-488-5p. RT-qPCR and Western blot were conducted to observe the expression of hsa_circ_0003528, miRNAs and CTLA4 in different patient and cell groups to establish the potential molecular mechanisms underlying the effect of hsa_circ_0003528 on M1 to M2 macrophage polarization.