Silencing of circRACGAP1 sensitizes gastric cancer cells to apatinib via modulating autophagy by targeting miR-3657 and ATG7
Identifieur interne : 000050 ( an2020/Analysis ); précédent : 000049; suivant : 000051Silencing of circRACGAP1 sensitizes gastric cancer cells to apatinib via modulating autophagy by targeting miR-3657 and ATG7
Auteurs : Ling Ma [République populaire de Chine] ; Zhangding Wang [République populaire de Chine] ; Mengyan Xie [République populaire de Chine] ; Yunlin Quan [République populaire de Chine] ; Weiyou Zhu [République populaire de Chine] ; Fengming Yang [République populaire de Chine] ; Chenhui Zhao [République populaire de Chine] ; Yu Fan [République populaire de Chine] ; Na Fang [République populaire de Chine] ; Huning Jiang [République populaire de Chine] ; Qiang Wang [République populaire de Chine] ; Shouyu Wang [République populaire de Chine] ; Jianwei Zhou [République populaire de Chine] ; Xiaofeng Chen [République populaire de Chine] ; Yongqian Shu [République populaire de Chine]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2020.
Abstract
The positive results of the apatinib phase III trial have cast new light on treatment for patients with advanced gastric cancer (GC). However, in terms of safety, apatinib toxicities may lead to a dose modification or treatment interruption. Therefore, proper intervention is urgently needed to help patients benefit from apatinib treatment. In this study, we found that apatinib promoted autophagy activation via upregulation of ATG7 expression and autophagy inhibition enhanced apatinib-induced apoptosis. With microRNA and circular RNA-sequencing analyses of GC xenograft models, we demonstrated that
Url:
DOI: 10.1038/s41419-020-2352-0
PubMed: 32139670
PubMed Central: 7058073
Affiliations:
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PMC:7058073Le document en format XML
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Zhangding" sort="Wang, Zhangding" uniqKey="Wang Z" first="Zhangding" last="Wang">Zhangding Wang</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1800 1685</institution-id><institution-id institution-id-type="GRID">grid.428392.6</institution-id><institution>Department of Gastroenterology,</institution><institution>The Affiliated Drum Tower Hospital of Nanjing University Medical School,</institution></institution-wrap>Nanjing, Jiangsu Province China</nlm:aff><wicri:noCountry code="subfield">Jiangsu Province China</wicri:noCountry></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9255 8984</institution-id><institution-id institution-id-type="GRID">grid.89957.3a</institution-id><institution>Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health,</institution><institution>Nanjing Medical University,</institution></institution-wrap>Nanjing, 211166 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Xie, Mengyan" sort="Xie, Mengyan" uniqKey="Xie M" first="Mengyan" last="Xie">Mengyan Xie</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Quan, Yunlin" sort="Quan, Yunlin" uniqKey="Quan Y" first="Yunlin" last="Quan">Yunlin Quan</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1761 0489</institution-id><institution-id institution-id-type="GRID">grid.263826.b</institution-id><institution>School of Mechanical Engineering, Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments,</institution><institution>Southeast University,</institution></institution-wrap>Nanjing, 211189 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Zhu, Weiyou" sort="Zhu, Weiyou" uniqKey="Zhu W" first="Weiyou" last="Zhu">Weiyou Zhu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Fengming" sort="Yang, Fengming" uniqKey="Yang F" first="Fengming" last="Yang">Fengming Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Zhao, Chenhui" sort="Zhao, Chenhui" uniqKey="Zhao C" first="Chenhui" last="Zhao">Chenhui Zhao</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Fan, Yu" sort="Fan, Yu" uniqKey="Fan Y" first="Yu" last="Fan">Yu Fan</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.452247.2</institution-id><institution>Cancer Institute, The Affiliated People’s Hospital of Jiangsu University,</institution></institution-wrap>Zhenjiang, 212002 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Zhenjiang</wicri:regionArea></affiliation></author><author><name sortKey="Fang, Na" sort="Fang, Na" uniqKey="Fang N" first="Na" last="Fang">Na Fang</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.452247.2</institution-id><institution>Cancer Institute, The Affiliated People’s Hospital of Jiangsu University,</institution></institution-wrap>Zhenjiang, 212002 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Zhenjiang</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Huning" sort="Jiang, Huning" uniqKey="Jiang H" first="Huning" last="Jiang">Huning Jiang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Qiang" sort="Wang, Qiang" uniqKey="Wang Q" first="Qiang" last="Wang">Qiang Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9255 8984</institution-id><institution-id institution-id-type="GRID">grid.89957.3a</institution-id><institution>Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health,</institution><institution>Nanjing Medical University,</institution></institution-wrap>Nanjing, 211166 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Shouyu" sort="Wang, Shouyu" uniqKey="Wang S" first="Shouyu" last="Wang">Shouyu Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9255 8984</institution-id><institution-id institution-id-type="GRID">grid.89957.3a</institution-id><institution>Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health,</institution><institution>Nanjing Medical University,</institution></institution-wrap>Nanjing, 211166 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Zhou, Jianwei" sort="Zhou, Jianwei" uniqKey="Zhou J" first="Jianwei" last="Zhou">Jianwei Zhou</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9255 8984</institution-id><institution-id institution-id-type="GRID">grid.89957.3a</institution-id><institution>Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health,</institution><institution>Nanjing Medical University,</institution></institution-wrap>Nanjing, 211166 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Xiaofeng" sort="Chen, Xiaofeng" uniqKey="Chen X" first="Xiaofeng" last="Chen">Xiaofeng Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>Pukou Branch Hospital of Jiangsu Province Hospital (Nanjing Pukou Central Hospital),</institution></institution-wrap>Nanjing, 211800 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author><author><name sortKey="Shu, Yongqian" sort="Shu, Yongqian" uniqKey="Shu Y" first="Yongqian" last="Shu">Yongqian Shu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1799 0784</institution-id><institution-id institution-id-type="GRID">grid.412676.0</institution-id><institution>Department of Oncology,</institution><institution>The First Affiliated Hospital of Nanjing Medical University,</institution></institution-wrap>Nanjing, 210029 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff7"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9255 8984</institution-id><institution-id institution-id-type="GRID">grid.89957.3a</institution-id><institution>Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine,</institution><institution>Nanjing Medical University,</institution></institution-wrap>Nanjing, 211166 China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Nanjing</wicri:regionArea></affiliation></author></analytic><series><title level="j">Cell Death & Disease</title><idno type="eISSN">2041-4889</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The positive results of the apatinib phase III trial have cast new light on treatment for patients with advanced gastric cancer (GC). However, in terms of safety, apatinib toxicities may lead to a dose modification or treatment interruption. Therefore, proper intervention is urgently needed to help patients benefit from apatinib treatment. In this study, we found that apatinib promoted autophagy activation via upregulation of ATG7 expression and autophagy inhibition enhanced apatinib-induced apoptosis. With microRNA and circular RNA-sequencing analyses of GC xenograft models, we demonstrated that <italic>circRACGAP1</italic> functioned as an endogenous sponge for <italic>miR-3657</italic> to inhibit its activity and further upregulate <italic>ATG7</italic> expression. Silencing of <italic>circRACGAP1</italic> inhibited apatinib-induced autophagy, which was rescued by <italic>miR-3657</italic>. Moreover, knockdown of <italic>circRACGAP1</italic> sensitized GC cells to apatinib via autophagy inhibition in vitro and in vivo. These findings provided the first evidence that the <italic>circRACGAP1</italic>-<italic>miR-3657-ATG7</italic> axis mediates a novel regulatory pathway critical for the regulation of apatinib sensitivity in GC. Thus, specific blockage of <italic>circRACGAP1</italic> may be a potential therapeutic strategy to reduce the toxicities of apatinib and enhance its therapeutic effect in human GC.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Bray, F" uniqKey="Bray F">F Bray</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, W" uniqKey="Chen W">W Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ychou, M" uniqKey="Ychou M">M Ychou</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambert, R" uniqKey="Lambert R">R Lambert</name></author><author><name sortKey="Saito, H" uniqKey="Saito H">H Saito</name></author><author><name sortKey="Lucas, E" uniqKey="Lucas E">E Lucas</name></author><author><name sortKey="Sankaranarayanan, R" uniqKey="Sankaranarayanan R">R 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Fang</name><name sortKey="Jiang, Huning" sort="Jiang, Huning" uniqKey="Jiang H" first="Huning" last="Jiang">Huning Jiang</name><name sortKey="Quan, Yunlin" sort="Quan, Yunlin" uniqKey="Quan Y" first="Yunlin" last="Quan">Yunlin Quan</name><name sortKey="Shu, Yongqian" sort="Shu, Yongqian" uniqKey="Shu Y" first="Yongqian" last="Shu">Yongqian Shu</name><name sortKey="Shu, Yongqian" sort="Shu, Yongqian" uniqKey="Shu Y" first="Yongqian" last="Shu">Yongqian Shu</name><name sortKey="Wang, Qiang" sort="Wang, Qiang" uniqKey="Wang Q" first="Qiang" last="Wang">Qiang Wang</name><name sortKey="Wang, Shouyu" sort="Wang, Shouyu" uniqKey="Wang S" first="Shouyu" last="Wang">Shouyu Wang</name><name sortKey="Wang, Zhangding" sort="Wang, Zhangding" uniqKey="Wang Z" first="Zhangding" last="Wang">Zhangding Wang</name><name sortKey="Xie, Mengyan" sort="Xie, Mengyan" uniqKey="Xie M" first="Mengyan" last="Xie">Mengyan Xie</name><name sortKey="Yang, Fengming" sort="Yang, Fengming" uniqKey="Yang F" first="Fengming" last="Yang">Fengming Yang</name><name sortKey="Zhao, Chenhui" sort="Zhao, Chenhui" uniqKey="Zhao C" first="Chenhui" last="Zhao">Chenhui Zhao</name><name sortKey="Zhou, Jianwei" sort="Zhou, Jianwei" uniqKey="Zhou J" first="Jianwei" last="Zhou">Jianwei Zhou</name><name sortKey="Zhu, Weiyou" sort="Zhu, Weiyou" uniqKey="Zhu W" first="Weiyou" last="Zhu">Weiyou Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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