Reduced microRNA-503 expression augments lung fibroblast VEGF production in chronic obstructive pulmonary disease

Ikari, Jun; Nelson, Amy; Obaid, Jannah M.; Girón-Martínez, Álvaro; Ikari, Kumiko; Makino, Fumihiko; Iwasawa, Shunichiro; Gunji, Yoko; Farid, Maha; Wang, Xingqi; Basma, Hesham; DeMeo, Dawn L.; Feghali‐Bostwick, Carol; Holz, Olaf; Rabe, Klaus F.; Liu, Xiangde; Rennard, Stephen I.

doi:10.1371/journal.pone.0184039

Cited by 17 publications

(9 citation statements)

References 45 publications

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“…13,24,27 A previous study has reported that miR-503 regulates the release of VEGF in COPD. 28 Our results confirmed that miR-503 inhibitor promoted glioma proliferation, migration, angiogenesis, and VEGFA expression; however, bevacizumab, as a VEGF inhibitor, could significantly reverse the above changes induced by miR-503 inhibitor, indicating that miR-503 regulates glioma proliferation, migration, and angiogenesis through VEGFA ( Figure 4A-D). In addition, a series of molecular and genetic analyses have indicated that LRIG2 plays an important role in glioma through ERGF/VEGFA pathway, and the expression of LRIG2 is related to angiogenesis.…”

Section: Discussionsupporting

confidence: 78%

miR-503 Inhibits Proliferation, Migration, And Angiogenesis Of Glioma By Acting On VEGFA Through Targeting LRIG2

Sun¹,

Shu²,

Tao³

2019

CMAR

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Background: Glioma is a common malignant tumor of the human central nervous system, and the pathological characteristics include invasive growth, angiogenesis, and so on. Ectopic expression of miR-503 works as a critical factor in cancer cell proliferation, migration, and capillary-like tube formation. The potential mechanisms of miR-503 in angiogenesis of glioma cells are still not reported. Methods: The expression levels of miR-503, LRIG2, and VEGFA mRNA and protein were performed by quantitative reverse transcription-PCR or Western blot assay. Dual-Luciferase reporter gene assay was used to determine the interaction between miR-503 and LRIG2. The concentration of VEGFA was measured using the ELISA method. The cell proliferation, migration, and angiogenesis of cocultured HCMEC/D3 cells were analyzed by MTT assay, transwell detection, and tube formation assay, respectively. Results: The expression levels of LRIG2 and VEGFA were reduced in glioma cells with miR-503 overexpression and enhanced with miR-503 inhibition. Moreover, cell proliferation, migration, and angiogenesis of cocultured HCMEC/D3 cells were alleviated with miR-503 mimics transfection. VEGFA and miR-503 inhibitor promoted cell proliferation, cell migration, and angiogenesis. Luciferase reporter gene assay revealed that miR-503 could directly target LRIG2. Furthermore, knockdown of LRIG2 or addition of VEGF inhibitor bevacizumab could abrogate the effect of miR-503 inhibitor on VEGFA expression, as well as the promotion of cell proliferation, migration, and angiogenesis. Conclusion: MiR-503 mediated LRIG2 suppression and regulated the expression of VEGFA, thereby reducing cell proliferation, migration, and angiogenesis of glioma cells. These results provide new insight into the action mechanism of miR-503-modulated signaling pathway in angiogenesis of glioma cells.

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Section: Discussionsupporting

confidence: 78%

miR-503 Inhibits Proliferation, Migration, And Angiogenesis Of Glioma By Acting On VEGFA Through Targeting LRIG2

Sun¹,

Shu²,

Tao³

2019

CMAR

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“… 31 Blockage of miR-503 has been reported to augment the release of vascular endothelial growth factor from lung fibroblasts of COPD patients. 32 MiR-218-5p, which was significantly downregulated in COPD patients compared with nonsmokers, was recognized as a protective factor for COPD. 33 Furthermore, Shen et al 34 reported that miR-483-5p was capable of abrogating the TGF-β-mediated cell proliferation in pulmonary epithelial and fibroblast cell lines.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-based identification of potential microRNA biomarkers in frequent and non-frequent exacerbators of COPD

Liu

Xue

et al. 2018

COPD

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ObjectivesMicroRNAs (miRNAs) play essential roles in the development of COPD. In this study, we aimed to identify and validate potential miRNA biomarkers in frequent and non-frequent exacerbators of COPD patients using bioinformatic analysis.Materials and methodsThe candidate miRNA biomarkers in COPD were screened from Gene Expression Omnibus (GEO) dataset and identified using GEO2R online tool. Then, we performed bioinformatic analyses including target prediction, gene ontology (GO), pathway enrichment analysis and construction of protein–protein interaction (PPI) network. Furthermore, the expression of the identified miRNAs in peripheral blood monocular cells (PBMCs) of COPD patients was validated using quantitative real-time polymerase chain reaction (qRT-PCR).ResultsMiR-23a, miR-25, miR-145 and miR-224 were identified to be significantly downregulated in COPD patients compared with healthy controls. GO analysis showed the four miRNAs involved in apoptotic, cell differentiation, cell proliferation and innate immune response. Pathway analysis showed that the targets of these miRNAs were associated with p53, TGF-β, Wnt, VEGF and MAPK signal pathway. In healthy controls, the miR-25 and miR-224 levels were significantly decreased in smokers compared with nonsmokers (P<0.001 and P<0.05, respectively). In COPD patients, the levels of miR-23a, miR-25, miR-145 and miR-224 were associated with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. Notably, miR-23a and miR-145 were significantly elevated in non-frequent exacerbators compared with frequent exacerbators (P<0.05), and miR-23a showed higher area under the receiver–operator characteristic curve (AUROC) than miR-145 (0.707 vs 0.665, P<0.05).ConclusionMiR-23a, miR-25, miR-145 and miR-224 were associated with the development of COPD, and miR-23a might be a potential biomarker for discriminating the frequent exacerbators from non-frequent exacerbators.

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“…Decreased miR-503 function promotes the release of VEGF from lung fibroblasts, thereby mediating vascular homeostasis in patients with COPD. 33 VEGF can be used to diagnose COPD in healthy donors (HD), with better overall accuracy and Youden's index (YI), while IL-8 can be used to diagnose cancer in both HD and COPD patients. 34 The serum levels of VEGF and its soluble receptor sVEGF R2 are higher in COPD patients than that in the control; therefore, VEGF and sVEGF R1 may be involved in aberrant pulmonary vascular remodeling in COPD patients.…”

Section: Discussionmentioning

confidence: 99%

CYP1B1, VEGFA, BCL2, and CDKN1A Affect the Development of Chronic Obstructive Pulmonary Disease

Yang¹,

Yan²,

Hu³

et al. 2020

COPD

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Purpose: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by poor airflow. The purpose of this study was to explore the mechanisms involved in the development of COPD. Patients and Methods: The mRNA expression profile GSE100281, consisting of 79 COPD and 16 healthy samples, was acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between COPD samples and healthy samples were analyzed using the limma package. Functional enrichment analysis for the DEGs was carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Furthermore, DEG-compound pairs were predicted using the Comparative Toxicogenomics Database. The KEGG metabolite IDs corresponding to the compounds were also obtained through the MetaboAnalyst pipeline. Based on the diffusion algorithm, the metabolite network was constructed. Finally, the expression levels of key genes were determined using quantitative PCR (qPCR). Results: There were 594 DEGs identified between the COPD and healthy samples, including 242 upregulated and 352 downregulated genes. A total of 696 DEG-compound pairs, such as BCL2-C00469 (ethanol) and BCL2-C00389 (quercetin) pairs, were predicted. CYP1B1, VEGFA, BCL2, and CDKN1A were included in the top 10 DEG-compound pairs. Additionally, 57 metabolites were obtained. In particular, hsa04750 (inflammatory mediator regulation of TRP channels)-C00469 (ethanol) and hsa04152 (AMPK signaling pathway)-C00389 (quercetin) pairs were found in the metabolite network. The results of qPCR showed that the expression of CYP1B1, VEGFA, BCL2, and CDKN1A was consistent with that predicted using bioinformatic analysis. Conclusion: CYP1B1, VEGFA, BCL2, and CDKN1A may play important functions in the development and progression of COPD.

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Reduced microRNA-503 expression augments lung fibroblast VEGF production in chronic obstructive pulmonary disease

Cited by 17 publications

References 45 publications

<p>miR-503 Inhibits Proliferation, Migration, And Angiogenesis Of Glioma By Acting On VEGFA Through Targeting LRIG2</p>

<p>miR-503 Inhibits Proliferation, Migration, And Angiogenesis Of Glioma By Acting On VEGFA Through Targeting LRIG2</p>

Bioinformatics-based identification of potential microRNA biomarkers in frequent and non-frequent exacerbators of COPD

<p><em>CYP1B1</em>, <em>VEGFA</em>, <em>BCL2</em>, and <em>CDKN1A</em> Affect the Development of Chronic Obstructive Pulmonary Disease</p>

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