UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells
Objectives. Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance....
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creator | Guo, Jiwei An, Jiajia Di, Weihua Du, Jing Wang, Xiaohong Jin, Dan Wu, Yan Shao, Cuijie |
description | Objectives. Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance. Methods. The mRNA expression of UBE2C, ZEB1/2, ABCG2, and ERCC1 was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining. Cell proliferation was detected by CCK8 and MTT assays. Cell migration and invasion were analyzed by wound healing assay and Transwell assays. Promoter activities and gene transcription were analyzed by luciferase reporter assay. Results. In this study, we examined the effect of UBE2C and ZEB1/2 expression levels in DDP-resistant cells of NSCLC. We confirmed that aberrant expression of UBE2C and ZEB1/2 plays a critical role in repressing the DDP sensitivity to NSCLC cells. Additionally, knockdown of UBE2C significantly sensitized resistant cells to DDP by repressing the expression of ZEB1/2. Mechanistic investigations indicated that UBE2C transcriptionally regulated ZEB1/2 by accelerating promoter activity. This study revealed that ZEB1/2 promotes the epithelial mesenchymal transition and expression of ABCG2 and ERCC1 to participate in UBE2C-mediated NSCLC DDP-resistant cell progression, metastasis, and invasion. Conclusion. UBE2C may be a novel therapy target for NSCLC for sensitizing cells to the chemotherapeutic agent DDP. |
doi_str_mv | 10.1155/2019/8607859 |
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Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance. Methods. The mRNA expression of UBE2C, ZEB1/2, ABCG2, and ERCC1 was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining. Cell proliferation was detected by CCK8 and MTT assays. Cell migration and invasion were analyzed by wound healing assay and Transwell assays. Promoter activities and gene transcription were analyzed by luciferase reporter assay. Results. In this study, we examined the effect of UBE2C and ZEB1/2 expression levels in DDP-resistant cells of NSCLC. We confirmed that aberrant expression of UBE2C and ZEB1/2 plays a critical role in repressing the DDP sensitivity to NSCLC cells. Additionally, knockdown of UBE2C significantly sensitized resistant cells to DDP by repressing the expression of ZEB1/2. Mechanistic investigations indicated that UBE2C transcriptionally regulated ZEB1/2 by accelerating promoter activity. This study revealed that ZEB1/2 promotes the epithelial mesenchymal transition and expression of ABCG2 and ERCC1 to participate in UBE2C-mediated NSCLC DDP-resistant cell progression, metastasis, and invasion. Conclusion. UBE2C may be a novel therapy target for NSCLC for sensitizing cells to the chemotherapeutic agent DDP.</description><identifier>ISSN: 1687-8450</identifier><identifier>EISSN: 1687-8450</identifier><identifier>EISSN: 1687-8469</identifier><identifier>DOI: 10.1155/2019/8607859</identifier><identifier>PMID: 30693031</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Antibodies ; Breast cancer ; Cancer therapies ; Cell cycle ; Chemotherapy ; Cloning ; Deoxyribonucleic acid ; DNA ; Drug resistance ; Genes ; Kinases ; Lung cancer ; Proteins</subject><ispartof>Journal of oncology, 2019, Vol.2019 (2019), p.1-15</ispartof><rights>Copyright © 2019 Yan Wu et al.</rights><rights>Copyright © 2019 Yan Wu et al. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © 2019 Yan Wu et al. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-eb0907be0d779f5e5a1da4c19a59097135ede9eeaf28b07a4ed8ee2deeb7876b3</citedby><cites>FETCH-LOGICAL-c471t-eb0907be0d779f5e5a1da4c19a59097135ede9eeaf28b07a4ed8ee2deeb7876b3</cites><orcidid>0000-0003-1636-6499</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333017/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333017/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,4009,27902,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30693031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Izadpanah, Reza</contributor><contributor>Reza Izadpanah</contributor><creatorcontrib>Guo, Jiwei</creatorcontrib><creatorcontrib>An, Jiajia</creatorcontrib><creatorcontrib>Di, Weihua</creatorcontrib><creatorcontrib>Du, Jing</creatorcontrib><creatorcontrib>Wang, Xiaohong</creatorcontrib><creatorcontrib>Jin, Dan</creatorcontrib><creatorcontrib>Wu, Yan</creatorcontrib><creatorcontrib>Shao, Cuijie</creatorcontrib><title>UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells</title><title>Journal of oncology</title><addtitle>J Oncol</addtitle><description>Objectives. Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance. Methods. The mRNA expression of UBE2C, ZEB1/2, ABCG2, and ERCC1 was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining. Cell proliferation was detected by CCK8 and MTT assays. Cell migration and invasion were analyzed by wound healing assay and Transwell assays. Promoter activities and gene transcription were analyzed by luciferase reporter assay. Results. In this study, we examined the effect of UBE2C and ZEB1/2 expression levels in DDP-resistant cells of NSCLC. We confirmed that aberrant expression of UBE2C and ZEB1/2 plays a critical role in repressing the DDP sensitivity to NSCLC cells. Additionally, knockdown of UBE2C significantly sensitized resistant cells to DDP by repressing the expression of ZEB1/2. Mechanistic investigations indicated that UBE2C transcriptionally regulated ZEB1/2 by accelerating promoter activity. This study revealed that ZEB1/2 promotes the epithelial mesenchymal transition and expression of ABCG2 and ERCC1 to participate in UBE2C-mediated NSCLC DDP-resistant cell progression, metastasis, and invasion. Conclusion. UBE2C may be a novel therapy target for NSCLC for sensitizing cells to the chemotherapeutic agent DDP.</description><subject>Antibodies</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Chemotherapy</subject><subject>Cloning</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug resistance</subject><subject>Genes</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Proteins</subject><issn>1687-8450</issn><issn>1687-8450</issn><issn>1687-8469</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNqN0c-L1DAUB_AgivtDb54l4EXQOi9t0jQXYSeO68KgsDoXLyFtXnezdNLatLv435thxnX15CkP8uHLe3wJecHgHWNCLHJgalGVICuhHpFjVlYyq7iAxw_mI3IS4w1AyUGVT8lRAaUqoGDHpN0sV7mmF8HNDUaqfRw6O_lALzH6ONnQIL31ln5fLdkizz7ggMFhmOhmGPFq3tk-0L6lZ0t9nlMbHF1das1oivj8Va811dh18Rl50tou4vPDe0o2H1ff9Kds_eX8Qp-ts4ZLNmVYgwJZIzgpVStQWOYsb5iyQoGSrBDoUCHaNq9qkJajqxBzh1jLSpZ1cUre73OHud6ia9Kmo-3MMPqtHX-a3nrz90_w1-aqvzVlURTAZAp4fQgY-x8zxslsfWzSCTZgP0eTM6m4kJKJRF_9Q2_6eQzpPJNzkCXnTORJvd2rZuxjHLG9X4aB2RVodgWaQ4GJv3x4wD3-3VgCb_bg2gdn7_x_xmEy2No_mlW8BCh-AZCIqrI</recordid><startdate>2019</startdate><enddate>2019</enddate><creator>Guo, Jiwei</creator><creator>An, Jiajia</creator><creator>Di, Weihua</creator><creator>Du, Jing</creator><creator>Wang, Xiaohong</creator><creator>Jin, Dan</creator><creator>Wu, Yan</creator><creator>Shao, Cuijie</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>Hindawi Limited</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1636-6499</orcidid></search><sort><creationdate>2019</creationdate><title>UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells</title><author>Guo, Jiwei ; An, Jiajia ; Di, Weihua ; Du, Jing ; Wang, Xiaohong ; Jin, Dan ; Wu, Yan ; Shao, Cuijie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-eb0907be0d779f5e5a1da4c19a59097135ede9eeaf28b07a4ed8ee2deeb7876b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antibodies</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Chemotherapy</topic><topic>Cloning</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Drug resistance</topic><topic>Genes</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Jiwei</creatorcontrib><creatorcontrib>An, Jiajia</creatorcontrib><creatorcontrib>Di, Weihua</creatorcontrib><creatorcontrib>Du, Jing</creatorcontrib><creatorcontrib>Wang, Xiaohong</creatorcontrib><creatorcontrib>Jin, Dan</creatorcontrib><creatorcontrib>Wu, Yan</creatorcontrib><creatorcontrib>Shao, Cuijie</creatorcontrib><collection>الدوريات العلمية والإحصائية - e-Marefa Academic and Statistical Periodicals</collection><collection>معرفة - المحتوى العربي الأكاديمي المتكامل - e-Marefa Academic Complete</collection><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</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>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 Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content 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>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Jiwei</au><au>An, Jiajia</au><au>Di, Weihua</au><au>Du, Jing</au><au>Wang, Xiaohong</au><au>Jin, Dan</au><au>Wu, Yan</au><au>Shao, Cuijie</au><au>Izadpanah, Reza</au><au>Reza Izadpanah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells</atitle><jtitle>Journal of oncology</jtitle><addtitle>J Oncol</addtitle><date>2019</date><risdate>2019</risdate><volume>2019</volume><issue>2019</issue><spage>1</spage><epage>15</epage><pages>1-15</pages><issn>1687-8450</issn><eissn>1687-8450</eissn><eissn>1687-8469</eissn><abstract>Objectives. Cisplatin (DDP) is one of the most commonly used chemotherapeutic drugs for several cancers, including non-small-cell lung cancer (NSCLC). However, resistance to DDP eventually develops, limiting its further application. New therapy targets are urgently needed to reverse DDP resistance. Methods. The mRNA expression of UBE2C, ZEB1/2, ABCG2, and ERCC1 was analyzed by reverse transcription-polymerase chain reaction. The protein levels of these molecules were analyzed by Western blotting and immunofluorescent staining. Cell proliferation was detected by CCK8 and MTT assays. Cell migration and invasion were analyzed by wound healing assay and Transwell assays. Promoter activities and gene transcription were analyzed by luciferase reporter assay. Results. In this study, we examined the effect of UBE2C and ZEB1/2 expression levels in DDP-resistant cells of NSCLC. We confirmed that aberrant expression of UBE2C and ZEB1/2 plays a critical role in repressing the DDP sensitivity to NSCLC cells. Additionally, knockdown of UBE2C significantly sensitized resistant cells to DDP by repressing the expression of ZEB1/2. Mechanistic investigations indicated that UBE2C transcriptionally regulated ZEB1/2 by accelerating promoter activity. This study revealed that ZEB1/2 promotes the epithelial mesenchymal transition and expression of ABCG2 and ERCC1 to participate in UBE2C-mediated NSCLC DDP-resistant cell progression, metastasis, and invasion. Conclusion. UBE2C may be a novel therapy target for NSCLC for sensitizing cells to the chemotherapeutic agent DDP.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>30693031</pmid><doi>10.1155/2019/8607859</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-1636-6499</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies Breast cancer Cancer therapies Cell cycle Chemotherapy Cloning Deoxyribonucleic acid DNA Drug resistance Genes Kinases Lung cancer Proteins |
title | UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
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