Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma
Temozolomide (TMZ) resistance limits its use in glioblastoma (GBM). Exosomes can carry circular RNAs (circRNAs) to regulate chemoresistance. To date, the role of exosomal hsa_circ_0043949 (circ_0043949) in GBM resistance to TMZ is unclear. Relative expression of circ_0043949 in clinical samples, GBM...
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| Veröffentlicht in: | Metabolic brain disease 2022-12, Vol.37 (8), p.2979-2993 |
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| creator | Li, Xuzhao Wang, Nianhua Leng, Haibin Yuan, Huichun Xu, Lixin |
| description | Temozolomide (TMZ) resistance limits its use in glioblastoma (GBM). Exosomes can carry circular RNAs (circRNAs) to regulate chemoresistance. To date, the role of exosomal hsa_circ_0043949 (circ_0043949) in GBM resistance to TMZ is unclear. Relative expression of circ_0043949 in clinical samples, GBM cell lines, and exosomes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC
50
) of TMZ, cell proliferation, apoptosis, invasion, and migration were analyzed via MTT, EdU, flow cytometry, transwell, and wound-healing assays. Relative protein levels were evaluated by western blotting. Target relationship was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays. Exosomes were isolated by ultracentrifugation and verified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The effect of exosomal circ_0043949 on TMZ resistance was validated by xenograft assay. Higher expression of circ_0043949 was gained in TMZ-resistant GBM samples and cells. Inhibition of circ_0043949 reduced TMZ resistance via decreasing IC
50
of TMZ, repressing proliferation, invasion, migration, and inducing apoptosis in TMZ-resistant GBM cells. Circ_0043949 mediated integrinalpha1 (ITGA1) expression via function as a miR-876-3p sponge. Circ_0043949 was also upregulated in TMZ-resistant GBM cells-derived exosomes, and exosomal circ_0043949 increased the resistance of TMZ-resistant GBM cells to TMZ in xenograft models. TMZ-resistant GBM cells-derived exosomal circ_0043949 promoted TMZ resistance via upregulating ITGA1 expression via sequestering miR-876-3p, offering a potential target for the treatment of TMZ resistance in GBM. |
| doi_str_mv | 10.1007/s11011-022-01069-3 |
| format | Article |
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50
) of TMZ, cell proliferation, apoptosis, invasion, and migration were analyzed via MTT, EdU, flow cytometry, transwell, and wound-healing assays. Relative protein levels were evaluated by western blotting. Target relationship was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays. Exosomes were isolated by ultracentrifugation and verified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The effect of exosomal circ_0043949 on TMZ resistance was validated by xenograft assay. Higher expression of circ_0043949 was gained in TMZ-resistant GBM samples and cells. Inhibition of circ_0043949 reduced TMZ resistance via decreasing IC
50
of TMZ, repressing proliferation, invasion, migration, and inducing apoptosis in TMZ-resistant GBM cells. Circ_0043949 mediated integrinalpha1 (ITGA1) expression via function as a miR-876-3p sponge. Circ_0043949 was also upregulated in TMZ-resistant GBM cells-derived exosomes, and exosomal circ_0043949 increased the resistance of TMZ-resistant GBM cells to TMZ in xenograft models. TMZ-resistant GBM cells-derived exosomal circ_0043949 promoted TMZ resistance via upregulating ITGA1 expression via sequestering miR-876-3p, offering a potential target for the treatment of TMZ resistance in GBM.</description><identifier>ISSN: 0885-7490</identifier><identifier>EISSN: 1573-7365</identifier><identifier>DOI: 10.1007/s11011-022-01069-3</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Apoptosis ; Assaying ; Biochemistry ; Bioinformatics ; Biomedical and Life Sciences ; Biomedicine ; Brain cancer ; Cell culture ; Cell lines ; Cell proliferation ; Chemoresistance ; Exosomes ; Flow cytometry ; Glioblastoma ; Metabolic Diseases ; Nanoparticles ; Neurology ; Neurosciences ; Oncogenes ; Oncology ; Original Article ; Polymerase chain reaction ; Reverse transcription ; Sequestering ; Temozolomide ; Transmission electron microscopy ; Ultracentrifugation ; Western blotting ; Wound healing ; Xenografts ; Xenotransplantation</subject><ispartof>Metabolic brain disease, 2022-12, Vol.37 (8), p.2979-2993</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022. Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c352t-ea3669e681ff0a077219810e0a4afc6d522482892c1e223edbfbee5a816f9aa03</citedby><cites>FETCH-LOGICAL-c352t-ea3669e681ff0a077219810e0a4afc6d522482892c1e223edbfbee5a816f9aa03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11011-022-01069-3$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11011-022-01069-3$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Li, Xuzhao</creatorcontrib><creatorcontrib>Wang, Nianhua</creatorcontrib><creatorcontrib>Leng, Haibin</creatorcontrib><creatorcontrib>Yuan, Huichun</creatorcontrib><creatorcontrib>Xu, Lixin</creatorcontrib><title>Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma</title><title>Metabolic brain disease</title><addtitle>Metab Brain Dis</addtitle><description>Temozolomide (TMZ) resistance limits its use in glioblastoma (GBM). Exosomes can carry circular RNAs (circRNAs) to regulate chemoresistance. To date, the role of exosomal hsa_circ_0043949 (circ_0043949) in GBM resistance to TMZ is unclear. Relative expression of circ_0043949 in clinical samples, GBM cell lines, and exosomes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC
50
) of TMZ, cell proliferation, apoptosis, invasion, and migration were analyzed via MTT, EdU, flow cytometry, transwell, and wound-healing assays. Relative protein levels were evaluated by western blotting. Target relationship was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays. Exosomes were isolated by ultracentrifugation and verified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The effect of exosomal circ_0043949 on TMZ resistance was validated by xenograft assay. Higher expression of circ_0043949 was gained in TMZ-resistant GBM samples and cells. Inhibition of circ_0043949 reduced TMZ resistance via decreasing IC
50
of TMZ, repressing proliferation, invasion, migration, and inducing apoptosis in TMZ-resistant GBM cells. Circ_0043949 mediated integrinalpha1 (ITGA1) expression via function as a miR-876-3p sponge. Circ_0043949 was also upregulated in TMZ-resistant GBM cells-derived exosomes, and exosomal circ_0043949 increased the resistance of TMZ-resistant GBM cells to TMZ in xenograft models. TMZ-resistant GBM cells-derived exosomal circ_0043949 promoted TMZ resistance via upregulating ITGA1 expression via sequestering miR-876-3p, offering a potential target for the treatment of TMZ resistance in GBM.</description><subject>Apoptosis</subject><subject>Assaying</subject><subject>Biochemistry</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain cancer</subject><subject>Cell culture</subject><subject>Cell lines</subject><subject>Cell proliferation</subject><subject>Chemoresistance</subject><subject>Exosomes</subject><subject>Flow cytometry</subject><subject>Glioblastoma</subject><subject>Metabolic Diseases</subject><subject>Nanoparticles</subject><subject>Neurology</subject><subject>Neurosciences</subject><subject>Oncogenes</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Polymerase chain reaction</subject><subject>Reverse transcription</subject><subject>Sequestering</subject><subject>Temozolomide</subject><subject>Transmission electron microscopy</subject><subject>Ultracentrifugation</subject><subject>Western blotting</subject><subject>Wound healing</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>0885-7490</issn><issn>1573-7365</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kEFr3DAQhUVpoNukf6AnQS-9OJ2RLNs6hpAmgUAuyVnMaseugi1tJTsk_fV1uoFADj0NPL73GD4hviKcIkD7oyACYgVKVYDQ2Ep_EBs0ra5a3ZiPYgNdZ6q2tvBJfC7lAQC0QbsRv64KOR-ydwC1trWVmUPsU_Zc5MxT-pPGNIUdr3kJZaboWT4Gkss-87CMNIc4yBR9GjiyvL67PENJT6HIEOUwhrQdqcxpohNx1NNY-MvrPRb3Py_uzq-qm9vL6_Ozm8pro-aKSTeN5abDvgeCtlVoOwQGqqn3zc4oVXeqs8ojK6V5t-23zIY6bHpLBPpYfD_s7nP6vXCZ3RSK53GkyGkpTrXKGqVrNCv67R36kJYc1-9WSjd2NYcvg-pA-ZxKydy7fQ4T5WeH4F7ku4N8t8p3_-Q7vZb0oVRWOA6c36b_0_oLYJaG5A</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Li, Xuzhao</creator><creator>Wang, Nianhua</creator><creator>Leng, Haibin</creator><creator>Yuan, Huichun</creator><creator>Xu, Lixin</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7U7</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20221201</creationdate><title>Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma</title><author>Li, Xuzhao ; Wang, Nianhua ; Leng, Haibin ; Yuan, Huichun ; Xu, Lixin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-ea3669e681ff0a077219810e0a4afc6d522482892c1e223edbfbee5a816f9aa03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Apoptosis</topic><topic>Assaying</topic><topic>Biochemistry</topic><topic>Bioinformatics</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain cancer</topic><topic>Cell culture</topic><topic>Cell lines</topic><topic>Cell proliferation</topic><topic>Chemoresistance</topic><topic>Exosomes</topic><topic>Flow cytometry</topic><topic>Glioblastoma</topic><topic>Metabolic Diseases</topic><topic>Nanoparticles</topic><topic>Neurology</topic><topic>Neurosciences</topic><topic>Oncogenes</topic><topic>Oncology</topic><topic>Original Article</topic><topic>Polymerase chain reaction</topic><topic>Reverse transcription</topic><topic>Sequestering</topic><topic>Temozolomide</topic><topic>Transmission electron microscopy</topic><topic>Ultracentrifugation</topic><topic>Western blotting</topic><topic>Wound healing</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Xuzhao</creatorcontrib><creatorcontrib>Wang, Nianhua</creatorcontrib><creatorcontrib>Leng, Haibin</creatorcontrib><creatorcontrib>Yuan, Huichun</creatorcontrib><creatorcontrib>Xu, Lixin</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolic brain disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Xuzhao</au><au>Wang, Nianhua</au><au>Leng, Haibin</au><au>Yuan, Huichun</au><au>Xu, Lixin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma</atitle><jtitle>Metabolic brain disease</jtitle><stitle>Metab Brain Dis</stitle><date>2022-12-01</date><risdate>2022</risdate><volume>37</volume><issue>8</issue><spage>2979</spage><epage>2993</epage><pages>2979-2993</pages><issn>0885-7490</issn><eissn>1573-7365</eissn><abstract>Temozolomide (TMZ) resistance limits its use in glioblastoma (GBM). Exosomes can carry circular RNAs (circRNAs) to regulate chemoresistance. To date, the role of exosomal hsa_circ_0043949 (circ_0043949) in GBM resistance to TMZ is unclear. Relative expression of circ_0043949 in clinical samples, GBM cell lines, and exosomes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The half-maximal inhibitory concentration (IC
50
) of TMZ, cell proliferation, apoptosis, invasion, and migration were analyzed via MTT, EdU, flow cytometry, transwell, and wound-healing assays. Relative protein levels were evaluated by western blotting. Target relationship was predicted by bioinformatics analysis and validated by dual-luciferase reporter and RNA pull-down assays. Exosomes were isolated by ultracentrifugation and verified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The effect of exosomal circ_0043949 on TMZ resistance was validated by xenograft assay. Higher expression of circ_0043949 was gained in TMZ-resistant GBM samples and cells. Inhibition of circ_0043949 reduced TMZ resistance via decreasing IC
50
of TMZ, repressing proliferation, invasion, migration, and inducing apoptosis in TMZ-resistant GBM cells. Circ_0043949 mediated integrinalpha1 (ITGA1) expression via function as a miR-876-3p sponge. Circ_0043949 was also upregulated in TMZ-resistant GBM cells-derived exosomes, and exosomal circ_0043949 increased the resistance of TMZ-resistant GBM cells to TMZ in xenograft models. TMZ-resistant GBM cells-derived exosomal circ_0043949 promoted TMZ resistance via upregulating ITGA1 expression via sequestering miR-876-3p, offering a potential target for the treatment of TMZ resistance in GBM.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s11011-022-01069-3</doi><tpages>15</tpages></addata></record> |
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| subjects | Apoptosis Assaying Biochemistry Bioinformatics Biomedical and Life Sciences Biomedicine Brain cancer Cell culture Cell lines Cell proliferation Chemoresistance Exosomes Flow cytometry Glioblastoma Metabolic Diseases Nanoparticles Neurology Neurosciences Oncogenes Oncology Original Article Polymerase chain reaction Reverse transcription Sequestering Temozolomide Transmission electron microscopy Ultracentrifugation Western blotting Wound healing Xenografts Xenotransplantation |
| title | Hsa_circ_0043949 reinforces temozolomide resistance via upregulating oncogene ITGA1 axis in glioblastoma |
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