Overexpression of VPS11 antagonizes the promoting effect of miR-542-3p on Mycobacterium tuberculosis survival in macrophages by regulating autophagy. (August 2022)

• Record Type: Journal Article
• Authors: Luo, Dan; Wu, Jialing; Liu, Yinyin; Li, Peng; Liang, Xianzhi; Xiao, Sifang; Qi, Zhiqiang; Liu, Ting; Pan, Jianhua
• Is Part Of: Microbial pathogenesis. Volume 169(2022)
• Publication Date: 2022-08
• Subjects: VPS11 -- miR-542-3p -- Tuberculosis -- Macrophages -- Autophagy; TB tuberculosis -- M.tb Mycobacterium tuberculosis -- IFN Interferon -- Eis enhanced intracellular survival -- 3′UTR 3′ untranslated region -- CFU Colony-forming unit -- RISC RNA-induced silencing complex -- HOPS homotypic fusion and protein sorting -- CORVET class C core vacuole/endosome tethering; Pathogenic microorganisms -- Periodicals; Pathology, Molecular -- Periodicals; Communicable Diseases -- microbiology -- Periodicals; Communicable Diseases -- parasitology -- Periodicals; Micro-organismes pathogènes -- Périodiques; Pathologie moléculaire -- Périodiques; Electronic journals; 616.9041
• DOI: 10.1016/j.micpath.2022.105609
• Languages: English
• ISSNs: 0882-4010

Abstract

Abstract: Impaired autophagy is an important cause of Mycobacterium tuberculosis survival in macrophages. VPS11 is an important regulator of autophagy; decreased VPS11 expression has been observed in macrophages after tuberculosis (TB) infection. Gene ontology data revealed that various miRNAs (for example, miR-542-3p) were upregulated in macrophages upon TB infection; thus, these miRNAs were likely to reduce VPS11 expression. In this study, both TB patients and healthy subjects were enrolled, and the levels of VPS11 and some miRNAs in their blood macrophages were measured. Moreover, various macrophages were cultured and infected with M. tuberculosis . Luciferase reporter, RNA pulldown, and RNA immunoprecipitation assays were performed to determine the regulatory effect of miR-542-3p on VPS11 expression. Results showed that VPS11 expression was downregulated, whereas miR-542-3p expression was upregulated in blood macrophages after TB infection. TB infection reduced VPS11 levels in two human macrophages in vitro, but not in mouse macrophages. This might be because the seed sequence exists in the VPS11 3' untranslated region in humans, but is absent in mice and rats. miR-542-3p promoted M. tuberculosis survival in human macrophages, but VPS11 overexpression antagonized the promoting effect of miR-542-3p. Further, VPS11 was confirmed as a target of miR-542-3p. Overexpression of VPS11 or depletion of miR-542-3p promoted autophagy, which was suppressed upon TB infection. In summary, VPS11 overexpression antagonized the promoting effect of miR-542-3p on M. tuberculosis survival in macrophages by regulating autophagy. Highlights: VPS11 expression was downregulated, whereas miR-542-3p expression was upregulated in blood macrophages after TB infection. VPS11 was confirmed as a target of miR-542-3p. TB infection reduced VPS11 levels in two human macrophages in vitro. miR-542-3p promoted M. tuberculosis survival in human macrophages, but VPS11 overexpression antagonized the promoting effect of miR-542-3p. Overexpression of VPS11 or depletion of miR-542-3p promoted autophagy, which was suppressed upon TB infection.