Open AccessUBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells
Author(s) -
Yan Wu,
Dayong Jin,
Xiaohong Wang,
Jing Du,
Weihua Di,
Jiajia An,
Cuijie Shao,
Jiwei Guo
Publication year - 2019
Publication title -
journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.228
H-Index - 54
eISSN - 1687-8469
pISSN - 1687-8450
DOI - 10.1155/2019/8607859
Subject(s) - cisplatin , gene knockdown , ercc1 , cancer research , downregulation and upregulation , gentamicin protection assay , luciferase , cell , cell growth , mtt assay , medicine , microbiology and biotechnology , biology , metastasis , cell culture , cancer , transfection , gene , chemotherapy , dna repair , biochemistry , genetics , nucleotide excision repair
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.