UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells

Figure 6

UBE2C increases the expression of ABCG2 and ERCC1 via regulating ZEB1/2 in DDP-resistant NSCLC cells. (a–c) A549/DDP cells were overexpressed or knockdown of UBE2C (a), ZEB1 (b), and ZEB2 (c), respectively. The mRNA and protein levels of ABCG2 and ERCC1 were analyzed by RT-PCR and western blot assay. (d, e) RT-PCR and Western blot result show that ZEB1 (d) or ZEB2 (e) dose-and time-dependently increased the protein level of ABCG2 and ERCC1 in A549/DDP cells. (f) The transcriptional activity of ABCG2 and ERCC1 regulated by ZEB1/2 was analyzed by luciferase reporter assay in A549/DDP cells. (g) The relationship between protein expression levels of ZEB1/2, ERCC1, and ABCG2 in 15 independent repetitive A549/DDP cells was analyzed based on western blot assay. (h, i) UBE2C increased the expression of ABCG2 and ERCC1 via regulation of ZEB1 (h) and ZEB2 (i) by RT-PCR and Western blot assay. (j) Schematic diagram of the mechanisms of UBE2C increased the drug resistance gene expression, ABCG2 and ERCC1, and the EMT progression via regulating ZEB1/2 expression in DDP-resistant NSCLC cells. Results were presented as mean ± SD, and the error bars represent the SD of three independent experiments. p<0.05; p<0.01 versus control group.

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