Can miRNA Indicate Risk of Illness after Continuous Exposure to M. tuberculosis?

Silva, Cleonardo Augusto; Gonçalves, Wanderson Gonçalves e; Pinto, Pablo Diego do Carmo; Pantoja, Rafael Pompeu; Vinasco-Sandoval, Tatiana; Ribeiro-dos-Santos, André M.; Hutz, Mara H.; Vidal, Amanda Ferreira; Araújo, Gilderlanio Santana de; Santos, Sidney Emanuel Batista dos

doi:10.3390/ijms22073674

Cited by 8 publications

(9 citation statements)

References 34 publications

(25 reference statements)

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“…The miR-4732-5p and miR-1255b-5p were also found to be elevated in ovarian cancer [47] ,breast cancer[48], and bladder cancer [49], respectively. It was reported that hsa-miR-486-3p and hsa-miR-4732-5p might be involved in immune modulation by regulating gene expression in immune cells [50]. However, the relationship between these miRNAs and tumor immune was not reported.…”

Section: Discussionmentioning

confidence: 98%

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Bao

Sun²,

Zhang

2022

Preprint

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Background: The immune microenvironment of lung cancer is complex, and T-cell tolerance is a primary mechanism of immune evasion. Tumor-derived exosomes (TEX) miRNAs regulate immune cells in tumor microenvironment (TME), contributing to tumor immune suppression. However, the underlying mechanisms remain unclear.Methods: TEX miRNA expression dataset (GSE111803) and CD8+ T cells mRNA expression profile (GSE90728) in lung adenocarcinoma (LUAD) were downloaded from Gene Expression Omnibus (GEO). The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were analyzed. The intersection of target genes of DEMs and DEGs was defined as the overlapped target genes. We performed the function and pathway analysis for DEGs and the overlapped genes by the DAVID tool and constructed a protein-protein interaction (PPI) network to screen modules and hub genes. Results: In total, 7 DEMs (5 upregulated and two downregulated miRNAs) and 672 DEGs (219 upregulated and 453 downregulated genes) were identified, then 185 overlapped genes for upregulated DEMs were selected for further analysis. GO analysis indicated the DEGs were mainly enriched in positive regulation of B cell activation, innate immune, while the overlapped genes were primarily involved in regulation of immune response. The pathway analysis suggested DEGs were primarily enriched in cytokine-cytokine receptor interaction, while the overlapped genes were primarily enriched in osteoclast differentiation. The PPI network revealed three significant modules for DEGs and the overlapped genes sets. These modules genes were mainly enriched in cell cycle, chemokine signaling pathway, and cytokine-cytokine receptor interaction, respectively.Conclusions: These results preliminarily revealed the mRNA expression profiles and the molecular regulatory mechanism of TEX miRNA regulated tumor immune response in LUAD.

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Section: Discussionmentioning

confidence: 98%

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Bao

Sun²,

Zhang

2022

Preprint

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“…Additionally, in terms of the hub-central genes identified in the brown module, several hub-central genes such as SRC (Chandra et al, 2016), ITGB3 (Chen et al, 2021a), BCL2L1 (Sharma et al, 2016), CDKN1A (Silva et al, 2021), MDM2 (Shariq et al, 2021) (Fang et al, 2020). Interestingly, research has reported that M. tuberculosis infection leads to upregulation of the SRC hub-central gene, which directly inhibits phagosomelysosome fusion and plays an effective role in maintaining mycobacterial survival within macrophages (Lechartier et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, in terms of the hub-central genes identified in the brown module, several hub-central genes such as SRC ( Chandra et al, 2016 ), ITGB3 ( Chen et al, 2021a ), BCL2L1 ( Sharma et al, 2016 ), CDKN1A ( Silva et al, 2021 ), MDM2 ( Shariq et al, 2021 ), and MMP1 ( Villarreal-Ramos et al, 2018 ) have been reported as key factors in the immunomodulatory mechanisms of MTBC agents such as M. bovis . It is well known that phagocytosis is an effective immune response process in killing intracellular mycobacteria, while mycobacteria prevent phagocytosis by host cells to maintain survival within macrophages ( Fang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, another study showed that, unlike the SRC hub-central gene, upregulation of the ITGB3 hub-central gene could overcome the inhibition of phagosome maturation due to mycobacterial infection, and activation of ITGB3 could facilitate M. tuberculosis clearance in vivo ( Chen et al, 2021a ). The BCL2L1 hub-central gene is an important anti-apoptotic factor that has shown a significant upregulation in response to M. bovis and M. tuberculosis infections, and it has been suggested that this hub-central gene plays a central role in the pathogenic mechanisms of infectious bacilli by inhibiting apoptosis ( Xaus et al, 1999 ; Nalpas et al, 2015 ; Silva et al, 2021 ). In addition to BCL2L1 , the CDKN1A hub-central gene encodes the p21 protein, a member of the Cip/Kip family, whose high levels are associated with pulmonary sarcoidosis and, as an inhibitor of apoptosis, facilitate the formation and maturation of TB granulomas ( Xaus et al, 1999 , 2003 ; Silva et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

et al. 2022

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ObjectiveBovine tuberculosis (bTB) is a chronic respiratory infectious disease of domestic livestock caused by intracellular Mycobacterium bovis infection, which causes ~$3 billion in annual losses to global agriculture. Providing novel tools for bTB managements requires a comprehensive understanding of the molecular regulatory mechanisms underlying the M. bovis infection. Nevertheless, a combination of different bioinformatics and systems biology methods was used in this study in order to clearly understand the molecular regulatory mechanisms of bTB, especially the immunomodulatory mechanisms of M. bovis infection.MethodsRNA-seq data were retrieved and processed from 78 (39 non-infected control vs. 39 M. bovis-infected samples) bovine alveolar macrophages (bAMs). Next, weighted gene co-expression network analysis (WGCNA) was performed to identify the co-expression modules in non-infected control bAMs as reference set. The WGCNA module preservation approach was then used to identify non-preserved modules between non-infected controls and M. bovis-infected samples (test set). Additionally, functional enrichment analysis was used to investigate the biological behavior of the non-preserved modules and to identify bTB-specific non-preserved modules. Co-expressed hub genes were identified based on module membership (MM) criteria of WGCNA in the non-preserved modules and then integrated with protein–protein interaction (PPI) networks to identify co-expressed hub genes/transcription factors (TFs) with the highest maximal clique centrality (MCC) score (hub-central genes).ResultsAs result, WGCNA analysis led to the identification of 21 modules in the non-infected control bAMs (reference set), among which the topological properties of 14 modules were altered in the M. bovis-infected bAMs (test set). Interestingly, 7 of the 14 non-preserved modules were directly related to the molecular mechanisms underlying the host immune response, immunosuppressive mechanisms of M. bovis, and bTB development. Moreover, among the co-expressed hub genes and TFs of the bTB-specific non-preserved modules, 260 genes/TFs had double centrality in both co-expression and PPI networks and played a crucial role in bAMs-M. bovis interactions. Some of these hub-central genes/TFs, including PSMC4, SRC, BCL2L1, VPS11, MDM2, IRF1, CDKN1A, NLRP3, TLR2, MMP9, ZAP70, LCK, TNF, CCL4, MMP1, CTLA4, ITK, IL6, IL1A, IL1B, CCL20, CD3E, NFKB1, EDN1, STAT1, TIMP1, PTGS2, TNFAIP3, BIRC3, MAPK8, VEGFA, VPS18, ICAM1, TBK1, CTSS, IL10, ACAA1, VPS33B, and HIF1A, had potential targets for inducing immunomodulatory mechanisms by M. bovis to evade the host defense response.ConclusionThe present study provides an in-depth insight into the molecular regulatory mechanisms behind M. bovis infection through biological investigation of the candidate non-preserved modules directly related to bTB development. Furthermore, several hub-central genes/TFs were identified that were significant in determining the fate of M. bovis infection and could be promising targets for developing novel anti-bTB therapies and diagnosis strategies.

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“…Comparative miRNA expression profiles in individuals with active tuberculosis and healthy controls were studied in an Amazon population. Three different miRNA expressions, hsa-miR-4732-5p, hsa-miR-486-3p, and hsa-let-7g-5p, were identified in tuberculosis patients ( Silva et al, 2021 ). However, different miRNA expressions can vary between individual samples during treatment and recovery ( Kleinsteuber et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Genetic Variants of MicroRNA and DROSHA Genes in Association With the Risk of Tuberculosis in the Amazon Population

et al. 2022

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Tuberculosis (TB) is a chronic infection caused by Mycobacterium tuberculosis (Mtb) with high incidence and mortality. Studies reported that host genetic variants might be associated with the risk of tuberculosis. The aim of this study was to perform an association study between 26 single nucleotide polymorphisms (SNPs) and tuberculosis and evaluate whether these SNPs may confer risk factors to tuberculosis in the Amazon population. There were 52 males and 126 females, with total of 178 healthy controls. Genotyping was performed using TaqMan Open Array Genotyping. Ancestry-informative markers were used to estimate the ancestral proportions of the individuals in the case and control groups. The results indicated that the SNPs rs10035440 (DROSHA), rs7372209 (miR26-a1), rs1834306 (miR100), rs4919510 (miR608), and rs10739971 (pri-let-7a-1) were significantly associated with high risk and rs3746444 (miR499) and rs6505162 (miR423), with low risk of developing tuberculosis in the Amazon population. Our study concluded that seven miRNA polymorphisms were associated with tuberculosis. Our study contributes to a better understanding of TB pathogenesis and may promote the development of new diagnostic tools against M. tuberculosis infection.

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Can miRNA Indicate Risk of Illness after Continuous Exposure to M. tuberculosis?

Cited by 8 publications

References 34 publications

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

Identification of Key Genes and Biological Pathways of Tumor-infiltrating CD8+ T Cell in Lung Adenocarcinoma

In-depth systems biological evaluation of bovine alveolar macrophages suggests novel insights into molecular mechanisms underlying Mycobacterium bovis infection

Genetic Variants of MicroRNA and DROSHA Genes in Association With the Risk of Tuberculosis in the Amazon Population

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