Cargando…
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....
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333017/ https://www.ncbi.nlm.nih.gov/pubmed/30693031 http://dx.doi.org/10.1155/2019/8607859 |
_version_ | 1783387483833106432 |
---|---|
author | Wu, Yan Jin, Dan Wang, Xiaohong Du, Jing Di, Weihua An, Jiajia Shao, Cuijie Guo, Jiwei |
author_facet | Wu, Yan Jin, Dan Wang, Xiaohong Du, Jing Di, Weihua An, Jiajia Shao, Cuijie Guo, Jiwei |
author_sort | Wu, Yan |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6333017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-63330172019-01-28 UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells Wu, Yan Jin, Dan Wang, Xiaohong Du, Jing Di, Weihua An, Jiajia Shao, Cuijie Guo, Jiwei J Oncol Research Article 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. Hindawi 2019-01-01 /pmc/articles/PMC6333017/ /pubmed/30693031 http://dx.doi.org/10.1155/2019/8607859 Text en Copyright © 2019 Yan Wu et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Wu, Yan Jin, Dan Wang, Xiaohong Du, Jing Di, Weihua An, Jiajia Shao, Cuijie Guo, Jiwei UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
title | UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
title_full | UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
title_fullStr | UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
title_full_unstemmed | UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
title_short | UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells |
title_sort | ube2c induces cisplatin resistance via zeb1/2-dependent upregulation of abcg2 and ercc1 in nsclc cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333017/ https://www.ncbi.nlm.nih.gov/pubmed/30693031 http://dx.doi.org/10.1155/2019/8607859 |
work_keys_str_mv | AT wuyan ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT jindan ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT wangxiaohong ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT dujing ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT diweihua ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT anjiajia ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT shaocuijie ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells AT guojiwei ube2cinducescisplatinresistanceviazeb12dependentupregulationofabcg2andercc1innsclccells |