CircAGFG1modulates autophagy and apoptosis of macrophages infected by Mycobacterium tuberculosis via the Notch signaling pathway

Background: Recent studies have revealed the involvement of circular RNAs (circRNAs) in the control and elimination of invading Mycobacterium tuberculosis (Mtb) by macrophages. However, the regulatory mechanism of circAGFG1 in macrophages infected by Mtb has not been fully explored. In this study, we sought to investigate the role of circAGFG1 on autophagy and apoptosis of Mtb-infected macrophages and reveal its the molecular mechanism.

Methods: The expression of circAGFG1 in macrophages from patients with active tuberculosis and in Mtb-treated macrophages in vitro was explored. Then, the effect of circAGFG1 on autophagy and apoptosis of Mtb-infected macrophages was evaluated by flow cytometry, electron microscope, immunofluorescence, and Western blotting. Bioinformatics analysis was used to identify and validate the downstream regulatory pathway of circAGFG1, miRNA-1257/Notch. For further analysis, the role of miRNA-1257 on autophagy and apoptosis was assessed.

Results: In vitro, ectopic expression of circAGFG1 upregulated autophagy and reduced apoptosis significantly in Mtb-infected cells. Notch levels were discovered to be increased by the silencing effect of circAGFG1 on miRNA-1257 expression. miRNA-1257 was found to noticeably reduce autophagy and promote macrophage apoptosis. Increased circAGFG1 expression, decreased monocyte apoptosis, and enhanced autophagy were found in macrophages from patients with active tuberculosis.

Conclusions: In active tuberculosis, circAGFG1 enhances autophagy and reduces apoptosis via the miRNA-1257/Notch axis; this provides new therapeutic targets for tuberculosis patients.