Acute 4,4′-Methylene Diphenyl Diisocyanate Exposure-Mediated Downregulation of miR-206-3p and miR-381-3p Activates Inducible Nitric Oxide Synthase Transcription by Targeting Calcineurin/NFAT Signaling in Macrophages

Lin, Chen-Chung; Law, Brandon F.; Hettick, Justin M.

doi:10.1093/toxsci/kfz215

Cited by 15 publications

(10 citation statements)

References 97 publications

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“…Our findings are consistent with the report that miR-206 expression was decreased in airway wall of a mouse model of childhood allergic asthma [57]. Recent studies showed that miR-206 expression was also decreased in mouse models of occupational asthma [58, 59]. In human, it was reported that circulating miR-206 was useful to predict childhood asthma exacerbation [60], and plasma miR-206 expression differed between asthmatics with higher and lower blood eosinophil counts [61].…”

Section: Discussionsupporting

confidence: 93%

An epithelial microRNA upregulates airway IL-25 and TSLP expression in type 2-high asthma via targeting CD39-extracellular ATP axis

Zhang

Feng

Liang

et al. 2020

Preprint

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The presence of type 2 inflammation is a prominent endotype of asthma. Airway epithelial cell-derived cytokines IL-25, IL-33 and TSLP initiate type 2 inflammation. However, the upstream signaling pathway regulating these cytokines expression remains elusive. We identified a small set of epithelial microRNAs differentially expressed between type 2-low and -high asthma patients. MiR-206 was the most highly expressed microRNA in type 2-high asthma relative to type 2-low asthma, but was downregulated in both asthma subsets compared to control subjects. CD39, an ecto-nucleotidase degrading extracellular ATP, was a target of miR-206 and upregulated in asthma. In cultured human bronchial epithelial cells, allergen-induced rapid accumulation of extracellular ATP was responsible for miR-206 downregulation and CD39 upregulation, suggesting a protective mechanism to eliminate excessive ATP. Importantly, BALF ATP levels were increased in asthma patients, and strongly correlated with elevated IL-25 and TSLP expression in type 2-high asthma. Intriguingly, inhibition of airway miR-206 increased Cd39 expression, suppressed airway ATP accumulation and Il-25, Il-33, Tslp expression, and alleviated type 2 inflammation in a mouse model of asthma. In contrast, airway miR-206 overexpression had opposite effects. Taken together, airway epithelial miR-206 upregulates IL-25, TSLP expression via targeting CD39-extracellular ATP axis in type 2-high asthma.

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Section: Discussionsupporting

confidence: 93%

An epithelial microRNA upregulates airway IL-25 and TSLP expression in type 2-high asthma via targeting CD39-extracellular ATP axis

Zhang

Feng

Liang

et al. 2020

Preprint

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“…Recently, studies on hsa-mir-206 have become a hot topic, but studies on AML are still lacking. Notably, we found that a recent study by Chen et al [25] on occupational asthma (OA) proposed a regulatory axis similar to that in this study. They pointed out that miR-206-3p, as a key factor in calcineurin/NFAT signaling in macrophages and bronchoalveolar lavage cells, affects the transcription of iNOS and thus regulates the development of OA.…”

Section: Discussionsupporting

confidence: 88%

Identification of prognostic biomarkers and potential regulatory axes for acute myeloid leukemia based on a competitive endogenous RNA network

Chen

et al. 2021

Preprint

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Background Acute myeloid leukemia (AML) is a common heterogeneous hematological malignancy with unclear pathogenesis and high mortality. Non-coding RNAs have recently received extensive attention. This study explored the potential mechanisms of interaction during the development of AML by analyzing a competitive endogenous RNA (ceRNA) network. Methods To obtain differentially expressed genes (DEGs), the transcripts and clinical AML data were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic analysis was used to predict the function annotation and RNA interaction. The data were used to construct a ceRNA regulatory network and survival analysis was used to discover key genes and predict potential regulatory axes. Quantitative Real-time PCR (qRT-PCR) was used to detect DEGs in HL-60 and THP-1 cell lines to verify the prediction. Results A ceRNA regulatory AML network with 164 lncRNA-miRNA-mRNA regulatory axes was constructed and visualized by Cytoscape software. Six lncRNAs were screened as potential prognostic factors for AML by survival analysis. Additionally, hsa-mir-206 and NFAT5 were discovered as key nodes in the ceRNA network. A CTB-193M12.1/hsa-mir-206/NFAT5 axis that was consistent with the ceRNA theory was identified. The qRT-PCR result showed that, compared with the normal control group, the expression of hsa-mir-206 in HL-60 and THP-1 cells was significantly decreased, while that of NFAT5 was moderately increased. Conclusions Therefore, the obtained ceRNA network and the CTB-193M12.1/hsa-mir-206/NFAT5 axis here may provide new view for exploring the pathogenic mechanisms of AML. NFAT5 and hsa-mir-206 were novel clinical predictors that may become key genes in AML.

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“…miRNA can regulate arginine metabolism by regulating the expression of key molecules in arginine metabolism pathway, such as ASS ( Bates et al, 2010 ; Tu et al, 2020 ), ARG1 ( Bates et al, 2010 ; Yoo et al, 2019 ), ARG2 ( Dunand-Sauthier et al, 2014 ; Jin et al, 2014 ; Kim et al, 2017 ; Wang Y. et al, 2017 ), CAT-1 ( Chang et al, 2004 ; Li Y. et al, 2018 ), ODC ( Jagannathan et al, 2015 ) and NOS ( Perske et al, 2010 ; Yan et al, 2011 ; Guo et al, 2012 ; Sun et al, 2012 ; Zhu et al, 2013 ; Li et al, 2014 , 2017 , Li H.T. et al, 2018 ; Fu et al, 2015 ; Jiang et al, 2015 ; Zhang et al, 2015 , 2020 ; Rasheed et al, 2016 ; Reilly et al, 2016 ; Muxel et al, 2017 , 2018 ; Wang C. et al, 2017 , Wang et al, 2019 ; Cui et al, 2020 ; Lin et al, 2020 ; Scalavino et al, 2020 ; Table 1 ). It has been found that multiple miRNAs could target the same enzyme or transporter protein, and the same molecule could also be regulated by multiple miRNAs.…”

Section: Mirnas and Long Non-coding Rnas In Arginine Metabolism And Crcmentioning

confidence: 99%

Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer

Han

2021

Front. Cell Dev. Biol.

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Colorectal cancer is the leading cause of death from cancer globally. The current treatment protocol still heavily relies on early detection and surgery. The molecular mechanisms underlying development of colorectal cancer are clinically important and determine the prognosis and treatment response. The arginine metabolism pathway is hyperactive in colorectal cancer and several molecules involved in the pathway are potential targets for chemoprevention and targeted colorectal cancer therapy. Endothelial nitric oxide synthase (eNOS), argininosuccinate synthetase and ornithine decarboxylase (ODC) are the main enzymes for arginine metabolism. Limiting arginine-rich meat consumption and inhibiting ODC activity largely reduces polyamine synthesis and the incidence of colorectal cancer. Arginine transporter CAT-1 and Human member 14 of the solute carrier family 6 (SLC6A14) are overexpressed in colorectal cancer cells and contributes to intracellular arginine levels. Human member 9 of the solute carrier family 38 (SLC38A9) serves as a component of the lysosomal arginine-sensing machinery. Pharmaceutical inhibition of single enzyme or arginine transporter is hard to meet requirement of restoring of abnormal arginine metabolic network. Apart from application in early screening for colorectal cancer, microRNA-based therapeutic strategy that simultaneously manipulating multiple targets involved in arginine metabolism brings promising future in the treatment of colorectal cancer.

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Acute 4,4′-Methylene Diphenyl Diisocyanate Exposure-Mediated Downregulation of miR-206-3p and miR-381-3p Activates Inducible Nitric Oxide Synthase Transcription by Targeting Calcineurin/NFAT Signaling in Macrophages

Cited by 15 publications

References 97 publications

An epithelial microRNA upregulates airway IL-25 and TSLP expression in type 2-high asthma via targeting CD39-extracellular ATP axis

An epithelial microRNA upregulates airway IL-25 and TSLP expression in type 2-high asthma via targeting CD39-extracellular ATP axis

Identification of prognostic biomarkers and potential regulatory axes for acute myeloid leukemia based on a competitive endogenous RNA network

Arginine Metabolism and Its Potential in Treatment of Colorectal Cancer

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