MicroRNA-142-3p inhibits autophagy and promotes intracellular survival of Mycobacterium tuberculosis by targeting ATG16L1 and ATG4c.
Int Immunopharmacol
; 101(Pt A): 108202, 2021 Dec.
Article
em En
| MEDLINE
| ID: mdl-34619495
ABSTRACT
BACKGROUND:
Mycobacterium tuberculosis (M. tuberculosis), which parasitizes host macrophages and lead to cellular immunologic responses, such as autophagy and apoptosis. Several studies had indicated that autophagy played important roles in alleviating intracellular survival of M. tuberculosis by accelerating the maturation of phagosome. Previously, we found miR-142-3p was significantly down-regulated in the macrophages after infection with M. tuberculosis. However, the role of miR-142-3p in the regulation of autophagy and M. tuberculosis survival is elusive.METHODS:
Bioinformatics analysis was used to obtain target genes of miR-142-3p; the binding sites of ATG16L1 and ATG4c were further confirmed with dual luciferase reporter assay; RAW264.7 cells were infected with H37Ra and the expression of miR-142-3p was measured by qRT-PCR; the autophagic marker protein was detected by western blot as well as immunofluorescence microscopy and transmission electron microscopes analysis.RESULTS:
Overexpression of miR-142-3p significantly inhibited H37Ra-induced activation of autophagy, blocked the maturation of phagosome in macrophages and promoted M. tuberculosis survival in macrophages. Furthermore, miR-142-3p negatively-regulated expression of ATG16L1 and ATG4c by directly targeting its 3'-UTR, and meaningfully abated the level of autophagy.CONCLUSION:
These findings suggested that miR-142-3p inhibited M. tuberculosis-induced activation of autophagy and promoted H37Ra survival in RAW264.7 cells by targeting ATG16L1 and ATG4c.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Cisteína Endopeptidases
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MicroRNAs
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Proteínas Relacionadas à Autofagia
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Mycobacterium tuberculosis
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2021
Tipo de documento:
Article