UBE2C Induces Cisplatin Resistance via ZEB1/2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cells
Authors: Weihua Di
Yan Wu
Jing Du
Dan Jin
Cuijie Shao
Jiwei Guo
Jiajia An
Xiaohong Wang
Journal: Journal of Oncology (2019)
Discipline: CLINICAL MEDICINE
Keywords: Cisplatin; DDP resistance; UBE2C; ZEB1/2; NSCLC
Affiliations: Cancer Research Institute, Binzhou Medical University Hospital, Binzhou 256603, China., Department of Pain Medicine, Binzhou Medical University Hospital, Binzhou 256603, China., Department of Thyroid and Breast Surgery, Binzhou Medical University Hospital, Binzhou 256603, China., Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou 256603, China.

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. 

Retracted: No

PubPeer comments:
 There seems to be dublication mRNA loading controls between Fig. 1 and 3. There is an overwhelming numbers of overlapping patterns in the scratching assay of Fig. 5  , 
 In the article titled u201cUBE2C Induces Cisplatin Resistance via ZEB1 2-Dependent Upregulation of ABCG2 and ERCC1 in NSCLC Cellsu201d [1], there is a concern of figure issue. In Figure 5(c), the wound healing images of PBS treatment were unintentionally misused for the control, siUBE2C, siUBE2Cu2009+u2009ZEB1, and UBE2C treatments in the groups of 0u2009h. In addition, the wound healing image of siUBE2C treatment was unintentionally misused for the UBE2Cu2009+u2009siZEB1 treatment in the groups of 36u2009h. The only change is in the panel of Figure 5(c), and the rest of the figure is identical to the published version. This unintentional error also has no bearing on the worku2019s scientific conclusions in any way. The authors apologize to the Editor of Journal of Oncology and to the readership for any inconvenience caused. The corrected figure and legend are presented here.  , 
 Two sets of images in Figure 5d appear to overlap. There are a number of similar issues that have led to retractions and corrections in papers with at least [one common author] . ***  ,