USP22 promotes the G1/S phase transition by upregulating FoxM1 expression via Œ≤-catenin nuclear localization and is associated with poor prognosis in stage II pancreatic ductal adenocarcinoma
Authors: Aman Wang
Zhongyu Wang
Jinxiao Liang
Zhen Ning
Yunpeng Xie
Lu Feng
Qiu Yan
Jiwei Liu
Journal: International Journal of Oncology (2014)
Discipline: CLINICAL MEDICINE
Keywords: USP22; FoxM1; pancreatic ductal adenocarcinoma; cell cycle regulation; tumorigenesis
Affiliations: Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China., Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China., Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, P.R. China., Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, P.R. China.

Abstract:  Ubiquitin-specific protease 22 (USP22), a newly discovered member of ubiquitin hydrolase family, exhibits a critical function in cell cycle progression and tumorigenesis. The forkhead box M1 (FoxM1) transcription factor plays a crucial role in cell proliferation, differentiation and transformation. However, the expression and functions of USP22 in pancreatic ductal adenocarcinoma (PDA) and whether FoxM1 is involved in USP22-mediated cell cycle regulation have not been studied. We examined the expression of USP22 and FoxM1 in 136 stage II PDA tissues by immunohistochemistry. Clinical significance was analyzed by multivariate Cox regression analysis, Kaplan-Meier curves and log-rank test. RT-PCR, western blot analysis, luciferase and immunofluorescence assays were used to investigate the molecular function of USP22 and FoxM1 in PDA fresh tissues and cell lines. USP22 and FoxM1 were significantly upregulated in PDA tissues compared with the paired normal carcinoma-adjacent tissues. A statistical correlation was observed between USP22 and FoxM1 expression. The expression of USP/FoxM1 and co-expression of both factors correlated with tumor size, lymph node metastasis and overall survival. Multivariate Cox regression analysis revealed that the expression of USP22/FoxM1, especially the co-expression of both factors, is an independent, unfavorable prognostic factor. USP22 overexpression is accompanied by an increase in FoxM1 expression and USP22 increases FoxM1 expression to promote G1/S transition and cell proliferation through promoting Œ≤-catenin nuclear translocation in PDA cell lines. USP22 promotes the G1/S phase transition by upregulating FoxM1 expression via promoting Œ≤-catenin nuclear localization. USP22 and FoxM1 may act as prognostic markers and potential targets for PDA. 

Retracted: No

PubPeer comments:
 Figure 4 . Much more similar than you would expect. , 
 Figure 4 . Much more similar than you would expect. , 
 I agree with comment #1 (and thus also with #2), and came here to post the same thing. In addition, two lanes in Figure 3D look remarkably similar to two lanes in Figure 5C, where they represent different experiments. Note a small white speck below and to the right of the right band. Shown with green boxes.  , 
 Corrigendum, September 2019 : https: www.spandidos-publications.com ijo 55 5 1176  Subsequently to the publication of the above paper, the authors have realized that Figs. 3 and 4 contained errors. Two sets of bands in Figs. 3D and 4B were erroneously placed during the process of figure preparation. In Fig. 3D, the u03b2-actin bands for the PANC-1 and CFPAC-1 cells were presented incorrectly, whereas in Fig.4B, the cdk4 bands for the CFPAC-1 cells were incorrect. The corrected versions of Figs. 3 and 4, showing the correct data for the u03b2-actin bands in Fig. 3D and the cdk4 bands for the CFPAC-1 cells in Fig. 4B, are shown opposite.  Note that these changes do not affect the interpretation of the data or the conclusions reported in this paper, and all the authors agree to this correction. The authors apologize to the Editor and to the readership of the Journal for any inconvenience caused. ,