Down-regulation of hsa_circ_0045474 induces macrophage autophagy in tuberculosis via miR-582-5p/TNKS2 axis

Macrophage autophagy plays a major role in the control and elimination of invading Mycobacterium tuberculosis. However, the function and mechanism of circRNA on macrophage autophagy in tuberculosis remain unclear. Therefore, this study aimed to explore the role of circRNA underlying macrophage autophagy in tuberculosis. Quantitative real-time polymerase chain reaction was used to detect the expression of hsa_circ_0045474, miR-582-5p and TNKS2. Autophagy was detected by LC3B immunofluorescence and transmission electron microscopy. Dual-luciferase reporter assays were used to detect the relationship of miR-582-5p and hsa_circ_0045474 or TNKS2. Western blot was used to detect the expression of LC3-CYRILLIC CAPITAL LETTER BYELORUSSIAN-UKRAINIAN I and LC3-CYRILLIC CAPITAL LETTER BYELORUSSIAN-UKRAINIAN ICYRILLIC CAPITAL LETTER BYELORUSSIAN-UKRAINIAN I. The results showed that hsa_circ_0045474 was down-regulated in monocytes from patients with tuberculosis and induced autophagy in macrophages. hsa_circ_0045474 sponged miR-582-5p and negatively regulated miR-582-5p expression. Overexpression of miR-582-5p affected by hsa_circ_0045474 induced autophagy in macrophages. TNKS2 served as a target of miR-582-5p and down-regulation of TNKS2 induced autophagy in macrophages regulated by miR-582-5p. In conclusion, our results demonstrated that hsa_circ_0045474 down-regulation induced macrophage autophagy in tuberculosis via miR-582-5p/ TNKS2 axis, implying a novel strategy to treat the occurrence of active pulmonary tuberculosis caused by immune escape of M. tuberculosis.