The Biological-Behavioral Effect Of Neuritin On Non-Small Cell Lung Cancer Vascular Endothelial Cells Via VEGFR And Notch1
Identifieur interne : 000742 ( Pmc/Curation ); précédent : 000741; suivant : 000743The 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.
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DOI: 10.2147/OTT.S212771
PubMed: 31819478
PubMed Central: 6876221
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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></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31819478</idno><idno type="pmc">6876221</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6876221</idno><idno type="RBID">PMC:6876221</idno><idno type="doi">10.2147/OTT.S212771</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000742</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" 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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><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Onco Targets Ther</journal-id><journal-id journal-id-type="iso-abbrev">Onco Targets Ther</journal-id><journal-id journal-id-type="publisher-id">OTT</journal-id><journal-id journal-id-type="pmc">ott</journal-id><journal-title-group><journal-title>OncoTargets and therapy</journal-title></journal-title-group><issn pub-type="epub">1178-6930</issn><publisher><publisher-name>Dove</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31819478</article-id><article-id pub-id-type="pmc">6876221</article-id><article-id pub-id-type="publisher-id">212771</article-id><article-id pub-id-type="doi">10.2147/OTT.S212771</article-id><article-categories><subj-group subj-group-type="heading"><subject>Original Research</subject></subj-group></article-categories><title-group><article-title>The Biological-Behavioral Effect Of Neuritin On Non-Small Cell Lung Cancer Vascular Endothelial Cells Via VEGFR And Notch1</article-title><alt-title alt-title-type="running-authors">Zhang et al</alt-title><alt-title alt-title-type="running-title">Zhang et al</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Qiao</given-names></name><xref ref-type="aff" rid="AFF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Juan</given-names></name><xref ref-type="aff" rid="AFF0002">2</xref></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Jian</given-names></name><xref ref-type="aff" rid="AFF0003">3</xref></contrib><contrib contrib-type="author"><name><surname>Aerxiding</surname><given-names>Patiguli</given-names></name><xref ref-type="aff" rid="AFF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Quhai</surname><given-names>Amina</given-names></name><xref ref-type="aff" rid="AFF0001">1</xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Cuncun</given-names></name><xref ref-type="corresp" rid="AN0001"></xref><xref ref-type="aff" rid="AFF0004">4</xref></contrib><contrib contrib-type="author"><name><surname>Shan</surname><given-names>Li</given-names></name><xref ref-type="corresp" rid="AN0002"></xref><xref ref-type="aff" rid="AFF0001">1</xref></contrib><aff id="AFF0001"><label>1</label><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></aff><aff id="AFF0002"><label>2</label><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></aff><aff id="AFF0003"><label>3</label><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></aff><aff id="AFF0004"><label>4</label><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></aff></contrib-group><author-notes><corresp id="AN0001">Correspondence: Cuncun Chen <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><phone>Tel +0991-7500419</phone><fax>Fax +860991-7860085</fax> Email chenpuyingxiong@yeah.net</corresp><corresp id="AN0002">Li Shan <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><phone>Tel +8613609989394</phone><fax>Fax +860991-7819342</fax> Email shanlinew319@163.com</corresp></author-notes><pub-date pub-type="epub"><day>20</day><month>11</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>12</volume><fpage>9747</fpage><lpage>9755</lpage><history><date date-type="received"><day>18</day><month>4</month><year>2019</year></date><date date-type="accepted"><day>06</day><month>9</month><year>2019</year></date></history><permissions><copyright-statement>© 2019 Zhang et al.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder>Zhang et al.</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/"><license-p>This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at <ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link> and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</ext-link>). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (<ext-link ext-link-type="uri" xlink:href="https://www.dovepress.com/terms.php">https://www.dovepress.com/terms.php</ext-link>).</license-p></license></permissions><abstract><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></abstract><kwd-group kwd-group-type="author"><title>Keywords</title><kwd>neuritin</kwd><kwd>non-small cell lung cancer</kwd><kwd>Notch1</kwd><kwd>VEGF</kwd></kwd-group><counts><fig-count count="5"></fig-count><table-count count="1"></table-count><ref-count count="30"></ref-count><page-count count="9"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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