Has-miR-30c-1-3p inhibits macrophage autophagy and pro-motes Mycobacterium tuberculosis survival by targeting ATG4B and ATG9B

Autophagy is a widespread physiological process in the body, which also protects the host by degrading invading pathogens and harmful substances during pathological conditions. However, Mycobacterium tuberculosis (MTB) can affect the process of autophagy by regulating the expres-sion of microRNAs (miRNAs), allowing for immune evasion. In this study, we constructed a model of a strong virulent strain (H37Rv) infection in human macrophage cell line. Following H37Rv infection, we screened 14 differentially expressed miRNAs by RNA-seq and bioinformatics. We predicted and demonstrated that miR-30c-1-3p inhibits autophagy and promotes macrophage survival by targeting ATG4B and ATG9B during the infection process.Additionally, the intervention of miR-30c-1-3p mimics resulted in an increased bacterial load in macrophages, suggesting that MTB achieves immune evasion by upregulating miR-30c-1-3p during infection. In conclusion, our study provides a valuable target for the development of host-directed anti-tuberculosis therapy as well as a new diagnostic marker. Overall design: To investigate the effect of miRNAs expression on macrophage autophagy after macrophages were infected with Mycobacterium tuberculosis.Total RNA was extracted from THP-1 cells infected with H37Rv for 2h and blank control and subjected to RNA-seq to analyze differentially expressed miRNAs associated with autophagy.