The hsa_circ_0002371/hsa-miR-502-5p/ATG16L1 axis modulates the survival of intracellular Mycobacterium tuberculosis and autophagy in macrophages
Circular RNAs (circRNAs) play a critical role in pathological mechanisms of Mycobacterium tuberculosis (Mtb) and can be used as a new biomarker for active tuberculosis (ATB) diagnosis. Therefore, we identified significantly dysregulated circRNAs in ATB patients and healthy controls (HC) and explored its molecular mechanism. We found that hsa_circ_0002371 was significantly up-regulated in PBMCs of ATB patients and H37Rv- or BCG-infected THP-1 human macrophages. Functional experiments demonstrated that hsa_circ_0002371 inhibited autophagy of BCG-infected THP-1 human macrophages and promoted intracellular BCG survival rate. Mechanistically, hsa_circ_0002371 promoted the expression of hsa-miR-502-5p, and hsa_circ_0002371 overexpression-induced protective effects in BCG-infected THP-1 human macrophages was largely overturned by the inhibition of hsa-miR-502-5p. Notably, hsa-miR-502-5p inhibited autophagy via suppressing autophagy related 16 like 1 (ATG16L1) in BCG-infected macrophages and thus promoting intracellular BCG growth. In summation, hsa_circ_0002371 increased the suppression of hsa-miR-502-5p on ATG16L1 and inhibited autophagy to promote Mtb growth in macrophages. In Conclusion, our data suggested that hsa_circ_0002371 was significantly up-regulated in the PBMCs of ATB patients compared with HC. The hsa_circ_0002371/hsa-miR-502-5p/ATG16L1 axis promoted the survival of intracellular Mtb and inhibited autophagy in macrophages. Our findings suggested hsa_circ_0002371 could act as a potential diagnostic biomarker and therapeutic target. Overall design: To compare the differentially expressed circRNAs in healthy and active pulmonary tuberculosis patients.