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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Veröffentlicht in:Journal of oncology 2019, Vol.2019 (2019), p.1-15
Hauptverfasser: Guo, Jiwei, An, Jiajia, Di, Weihua, Du, Jing, Wang, Xiaohong, Jin, Dan, Wu, Yan, Shao, Cuijie
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container_end_page 15
container_issue 2019
container_start_page 1
container_title Journal of oncology
container_volume 2019
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. 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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. 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source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Wiley Online Library Open Access; PubMed Central; Alma/SFX Local Collection
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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