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MicroRNA‑502‑3p promotes Mycobacterium tuberculosis survival in macrophages by modulating the inflammatory response by targeting ROCK1

Liu, Fang ; Dong, Zhen ; Lin, Yuefu ; Yang, Haibo ; Wang, Pingping ; Zhang, Yongxia

Molecular medicine reports, 2021-11, Vol.24 (5), Article 753

Greece: Spandidos Publications

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Título:
MicroRNA‑502‑3p promotes Mycobacterium tuberculosis survival in macrophages by modulating the inflammatory response by targeting ROCK1
Autor: Liu, Fang ; Dong, Zhen ; Lin, Yuefu ; Yang, Haibo ; Wang, Pingping ; Zhang, Yongxia
Assuntos: Adolescent ; Adult ; Animals ; Binding sites ; Biotechnology ; Case-Control Studies ; Cell Line, Tumor ; Cell survival ; Cellular signal transduction ; Chromosome 3 ; Datasets ; Development and progression ; Down-Regulation - drug effects ; Down-Regulation - immunology ; Female ; Gene expression ; Genetic aspects ; Health aspects ; Healthy Volunteers ; Host-Pathogen Interactions - drug effects ; Host-Pathogen Interactions - genetics ; Humans ; IL-1β ; Immune response ; Immunocytochemistry ; Infections ; Infectious diseases ; Inflammation ; Interleukin 6 ; Kinases ; Macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages - microbiology ; Male ; Membranes ; Mice ; MicroRNA ; MicroRNAs ; MicroRNAs - agonists ; MicroRNAs - antagonists & inhibitors ; MicroRNAs - metabolism ; Middle Aged ; miRNA ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - immunology ; Mycobacterium tuberculosis - isolation & purification ; NF-κB protein ; Nuclear transport ; Plasmids ; Protein kinase ; Protein kinases ; Proteins ; RAW 264.7 Cells ; Reverse transcription ; rho-Associated Kinases - genetics ; rho-Associated Kinases - metabolism ; Signal transduction ; Signal Transduction - drug effects ; Signal Transduction - genetics ; Signal Transduction - immunology ; TLR4 protein ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Transcription Factor RelA - metabolism ; Transfection ; Tuberculosis ; Tuberculosis - blood ; Tuberculosis - genetics ; Tuberculosis - immunology ; Tuberculosis - microbiology ; Tumor necrosis factor-α ; Western blotting ; Young Adult
É parte de: Molecular medicine reports, 2021-11, Vol.24 (5), Article 753
Descrição: Tuberculosis (TB) is caused by infection and has the highest mortality rate of any single infectious disease worldwide. The aim of the present study was to investigate the function of microRNA (miR)‑502‑3p in ‑infected macrophages. The Gene Expression Omnibus database was used to analyze miR‑502‑3p expression in patients with TB and healthy individuals. THP‑1 and RAW 264.7 cells were transfected with miR‑502‑3p mimic, miR‑502‑3p inhibitor, pcDNA3.1‑ROCK1 or their negative controls. The expression levels of miR‑502‑3p and inflammatory cytokines were evaluated using reverse transcription‑quantitative PCR. The colony‑forming unit assay was performed to assess the survival of in macrophages, and Toll‑like receptor (TLR)4/NF‑κB signaling pathway‑associated protein expression levels were detected by western blotting. The nuclear translocation of NF‑κB p65 was detected via immunocytochemistry. TargetScan was used to predict the binding sites between miR‑502‑3p and ROCK1. The interaction between miR‑502‑3p and Rho‑associated coiled‑coil‑forming protein kinase 1 (ROCK1) was confirmed using a dual‑luciferase reporter assay; ROCK1 was demonstrated to be a direct target gene of miR‑502‑3p. Results from the present study demonstrated that miR‑502‑3p expression was significantly increased during infection in macrophages. Upregulation of miR‑502‑3p expression levels significantly enhanced the survival of intracellular . IL‑6, TNF‑α, and IL‑1β mRNA expression levels were significantly upregulated during infection but were downregulated by miR‑502‑3p overexpression. Moreover, miR‑502‑3p mimics transfection significantly downregulated TLR4/NF‑κB signaling pathway‑associated protein expression and significantly reduced nuclear transcription of NF‑κB in ‑infected macrophages. ROCK1 overexpression reversed the miR‑502‑3p inhibitory effect on cytokine production in ‑infected macrophages. In conclusion, miR‑502‑3p/ROCK1 may serve an anti‑inflammatory role and may improve the survival of within macrophages, which may provide a promising therapeutic target for TB.
Editor: Greece: Spandidos Publications
Idioma: Inglês

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MicroRNA‑502‑3p promotes Mycobacterium tuberculosis survival in macrophages by modulating the inflammatory response by targeting ROCK1

Liu, Fang ; Dong, Zhen ; Lin, Yuefu ; Yang, Haibo ; Wang, Pingping ; Zhang, Yongxia

Greece: Spandidos Publications

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