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Down-regulation of hsa_circ_0045474 induces macrophage autophagy in tuberculosis via miR-582-5p/TNKS2 axis
Innate Immunity ( IF 3.2 ) Pub Date : 2021-12-03 , DOI: 10.1177/17534259211064285
Min Wu 1 , Zhibin Liu 1 , Shaojun Zhang 1
Affiliation  

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-І and LC3-ІІ. 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.



中文翻译:

hsa_circ_0045474 的下调通过 miR-582-5p/TNKS2 轴诱导结核病中的巨噬细胞自噬

巨噬细胞自噬在控制和消灭入侵的结核杆菌中发挥重要作用. 然而,circRNA对结核病巨噬细胞自噬的作用及机制尚不清楚。因此,本研究旨在探讨巨噬细胞自噬背后的circRNA在结核病中的作用。采用定量实时聚合酶链反应检测hsa_circ_0045474、miR-582-5p和TNKS2的表达。通过 LC3B 免疫荧光和透射电子显微镜检测自噬。双荧光素酶报告基因检测用于检测 miR-582-5p 与 hsa_circ_0045474 或 TNKS2 的关系。Western blot检测LC3-І和LC3-ІІ的表达。结果表明,hsa_circ_0045474 在肺结核患者的单核细胞中下调,并在巨噬细胞中诱导自噬。hsa_circ_0045474 海绵化 miR-582-5p 并负调控 miR-582-5p 表达。受 hsa_circ_0045474 影响的 miR-582-5p 过表达诱导巨噬细胞自噬。TNKS2 充当 miR-582-5p 的靶标,下调 TNKS2 诱导的巨噬细胞自噬由 miR-582-5p 调节。总之,我们的研究结果表明,hsa_circ_0045474 下调通过 miR-582-5p/TNKS2 轴诱导结核病中的巨噬细胞自噬,这意味着一种治疗由免疫逃逸引起的活动性肺结核发生的新策略。结核分枝杆菌

更新日期:2021-12-04
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