The Biological-Behavioral Effect Of Neuritin On Non-Small Cell Lung Cancer Vascular Endothelial Cells Via VEGFR And Notch I
Purpose: This study aims to elucidate the biological behavior of Neuritin abnormal expression in pulmonary vascular endothelial cells (VECs) of non-small cell lung cancer (NSCLC), and explore its possible underlying mechanisms. Patients and methods: Primary NSCLC-VECs were isolated from 10 cancer ti...
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Published in | OncoTargets and therapy p. 9747 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Dove Medical Press Limited
01.11.2019
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Subjects | |
Online Access | Get full text |
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Summary: | Purpose: This study aims to elucidate the biological behavior of Neuritin abnormal expression in pulmonary vascular endothelial cells (VECs) of non-small cell lung cancer (NSCLC), and explore its possible underlying mechanisms. Patients and methods: Primary NSCLC-VECs were isolated from 10 cancer tissues from NSCLC patients, purified and identified by CD34 and Factor VIII staining. Real-time PCR and Western-blot were adopted for detecting the expression levels of Neuritin, Notch1, and VEGFR in NSCLC-VECs and HPMECs. Neuritin-overexpression, Neuritin-knockdown NSCLC-VECs and HPMECs were constructed by transfection of pcDNA3, 1-Neuritin vector, and pBS/U6-Neuritin siRNA. Changes in cell proliferation, migration, cell cycle, and apoptosis were determined by using the MTT assay, scratch assay, transwell migration assay, and flow cytometry, respectively. Post-transfection changes in cell morphology were examined by scanning electron microscopy. Results: The expression of Neuritin in NSCLC-VECs was significantly higher compared to that in HPMECs (p<0.01). Overexpression of Neuritin increased the expression of VEGFR while it reduced the expression of Notch1 (p<0.01); it also promoted cell proliferation, scratch healing, and in vitro migration (p<0.05) in HPMECs and NSCLC-VECs cells. Additionally, overexpression of Neuritin stimulated cell cycle progression and inhibited apoptosis in HPMECs and NSCLC-VECs (p<0.001). Under electron microscope, the pseudopodium of cell surface was obvious, indicating that the intercellular adhesion was upregulated. However, knockdown of Neuritin in HPMECs and NSCLC-VECs played exactly the opposite roles. Conclusion: Neuritin was key in the progression of NSCLC through its biological activities, including anti-apoptosis, promoting VEC proliferation, migration, and cell cycle progression. Neuritin may affect its biological activity by positively regulating VEGFR expression and negatively regulating Notch1 signaling. Neuritin may serve as a potential biomarker for NSCLC. Keywords: neuritin, non-small cell lung cancer, Notch1, VEGF |
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ISSN: | 1178-6930 1178-6930 |
DOI: | 10.2147/OTT.S212771 |