The Biological-Behavioral Effect Of Neuritin On Non-Small Cell Lung Cancer Vascular Endothelial Cells Via VEGFR And Notch1
Identifieur interne : 000367 ( Main/Exploration ); précédent : 000366; suivant : 000368The Biological-Behavioral Effect Of Neuritin On Non-Small Cell Lung Cancer Vascular Endothelial Cells Via VEGFR And Notch1
Auteurs : Qiao Zhang [République populaire de Chine] ; Juan Zhang [République populaire de Chine] ; Jian Zhang [République populaire de Chine] ; Patiguli Aerxiding [République populaire de Chine] ; Amina Quhai [République populaire de Chine] ; Cuncun Chen [République populaire de Chine] ; Li Shan [République populaire de Chine]Source :
- OncoTargets and therapy [ 1178-6930 ] ; 2019.
Abstract
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.
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.
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.
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.
Url:
DOI: 10.2147/OTT.S212771
PubMed: 31819478
PubMed Central: 6876221
Affiliations:
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sort="Aerxiding, Patiguli" uniqKey="Aerxiding P" first="Patiguli" last="Aerxiding">Patiguli Aerxiding</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Thoraciconcology, The Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical University</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line><addr-line>830011</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Quhai, Amina" sort="Quhai, Amina" uniqKey="Quhai A" first="Amina" last="Quhai">Amina Quhai</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Thoraciconcology, The Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical 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id="AFF0001"><institution>Department of Thoraciconcology, The Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical University</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line><addr-line>830011</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Juan" sort="Zhang, Juan" uniqKey="Zhang J" first="Juan" last="Zhang">Juan Zhang</name><affiliation wicri:level="1"><nlm:aff id="AFF0002"><institution>Department of Respiratory and Critical Care Medicine, First People’s Hospital of Kashgar</institution>,<addr-line>Xinjiang</addr-line><addr-line>844000</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><affiliation wicri:level="1"><nlm:aff id="AFF0003"><institution>Health Corps of the People's Liberation Army 69260 Troops</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line>,<addr-line>830002</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Aerxiding, Patiguli" sort="Aerxiding, Patiguli" uniqKey="Aerxiding P" first="Patiguli" last="Aerxiding">Patiguli Aerxiding</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Thoraciconcology, The Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical University</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line><addr-line>830011</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Quhai, Amina" sort="Quhai, Amina" uniqKey="Quhai A" first="Amina" last="Quhai">Amina Quhai</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Thoraciconcology, The Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical University</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line><addr-line>830011</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Cuncun" sort="Chen, Cuncun" uniqKey="Chen C" first="Cuncun" last="Chen">Cuncun Chen</name><affiliation wicri:level="1"><nlm:aff id="AFF0004"><institution>Department of Thoracic Surgery, Chest Hospital of Xinjiang Uyghur Autonomous Region</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line><addr-line>830049</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Shan, Li" sort="Shan, Li" uniqKey="Shan L" first="Li" last="Shan">Li Shan</name><affiliation wicri:level="1"><nlm:aff id="AFF0001"><institution>Department of Thoraciconcology, The Third Affiliated Hospital of Xinjiang Medical University, Tumor Hospital Affiliated to Xinjiang Medical University</institution>,<addr-line>Urumqi</addr-line>,<addr-line>Xinjiang</addr-line><addr-line>830011</addr-line>,<country>People’s Republic of China</country></nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">OncoTargets and therapy</title><idno type="eISSN">1178-6930</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S2001"><title>Purpose</title><p>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.</p></sec><sec id="S2002"><title>Patients and methods</title><p>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.</p></sec><sec id="S2003"><title>Results</title><p>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.</p></sec><sec id="S2004"><title>Conclusion</title><p>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.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Qiao" sort="Zhang, Qiao" uniqKey="Zhang Q" first="Qiao" last="Zhang">Qiao Zhang</name></noRegion><name sortKey="Aerxiding, Patiguli" sort="Aerxiding, Patiguli" uniqKey="Aerxiding P" first="Patiguli" last="Aerxiding">Patiguli Aerxiding</name><name sortKey="Chen, Cuncun" sort="Chen, Cuncun" uniqKey="Chen C" first="Cuncun" last="Chen">Cuncun Chen</name><name sortKey="Quhai, Amina" sort="Quhai, Amina" uniqKey="Quhai A" first="Amina" last="Quhai">Amina Quhai</name><name sortKey="Shan, Li" sort="Shan, Li" uniqKey="Shan L" first="Li" last="Shan">Li Shan</name><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name><name sortKey="Zhang, Juan" sort="Zhang, Juan" uniqKey="Zhang J" first="Juan" last="Zhang">Juan Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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