Research Paper Volume 12, Issue 24 pp 25658—25672

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

Zikun Huang1, *, , Fangyi Yao1, *, , Jun Liu1, , Jianqing Xu1, , Yang Guo1, , Rigu Su1, , Qing Luo1, , Junming Li1, ,

  • 1 Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, China
* Equal contribution

Received: June 15, 2020       Accepted: September 20, 2020       Published: December 9, 2020
How to Cite

Copyright: © 2020 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: In this study, we selected several candidate miRNAs to study their possible relationships with tuberculosis.

Results: 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.

Conclusion: 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.

Methods: 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.


HC: healthy control; TB: tuberculosis; CircRNA: Circular RNA; MiRNAs: MicroRNAs; TLRs: Toll-like receptors; CTLA-4: Cytotoxic T Lymphocyte-Associated Antigen 4; CeRNAs: Competing endogenous RNAs.