UBQLN4 promotes progression of HCC via activating wnt-β-catenin pathway and is regulated by miR-370
Authors: Xiaolong Chen
Xiaodong Xu
Guangying Cui
Yan Yu
Penglin Xu
Kongfei Li
Jie Bao
Journal: Cancer Cell International (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hepatocellular carcinoma (HCC); MiR-370; Ubiquilin-4 (UBQLN4); wnt-β-catenin pathway.
Affiliations: 1Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 China., 2Key Laboratory of Clinical Medicine, Department of Digestive Diseases, The First Affiliated Hospital of Zhengzhou University, 1# Jianshe East Road, Zhengzhou, 450052 China., 3Department of Hematology, Yinzhou People's Hospital Affiliated to Medical College of Ningbo University, Ningbo, China.

Abstract:  Background: Ubiquilin-4 (UBQLN4) is a member of the ubiquitin-proteasome system that is usually upregulated in many tumor cells. Its overexpression has been associated with poor disease outcomes in various cancer diseases. However, the underlying mechanism of UBQLN4 in the development of hepatocellular carcinoma (HCC) has not been elucidated. Methods: Immunochemistry, real-time PCR, and western blotting were used to evaluate the expression levels of UBQLN4 in cancer tissues. Univariate, Cox-regression, and Kaplan-Meier analyses were performed to determine the association between UBQLN4 expression and HCC prognosis. Cell Counting Kit-8 (CCK-8), transwell, EDU and colony formation assays were conducted to evaluate the role of UBQLN4 in HCC cell progression. The gene set enrichment analysis and luciferase reporter experiments were conducted to find the mechanism of UBQLN4 in HCC. Results: Ubiquilin-4 (UBQLN4) was overexpressed in HCC tissues. Besides, overexpression of UBQLN4 was associated with poor overall survival and disease-free survival rate of HCC patients. The loss-of-function analysis revealed that suppression of UBQLN4 inhibited the proliferation and invasion of HCC cells in vivo and in vitro. The KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that UBQLN4 could regulate activation of the wnt-β-catenin pathway in HCC cells. Furthermore, our results showed that UBQLN4 was downregulated by miR-370, which acted as a tumor suppressor gene in HCC progression. Conclusion: The results of the present study suggest that the miR-370/UBQLN4 axis may play a critical role in the progression of HCC. These findings may inform future strategies for the development of therapeutic agents against HCC. 

Retracted: No

PubPeer comments:
 Could the authors review the images in Figure 4g and 8d? I believe there may be some repeated images. *** ![file] , 
 #1 Dear Dr. Biskrensis, Thank you for pointing out the error of images of Figure 4G and 8D. We have carefully investigated our raw data. In the published Figure 4G and 8D, the transwell data in HepG2 group (Figure 4G ) were duplicated in HepG2 group (Figure 8D) because of mistake during the figure arrangement. We will make the following correction to Figure 4G in our paper. We confirm that neither of these changes affects the results and conclusions of this study. We will apply to the editor of Cancer Cell internation to help us correct the misplaced pictures. We sincerely apologize for the mistake. We thank the reader again and thank the staff working for PubPeer very much! Best regardsu00a0 Yan Yu , 
 #2 Thank you for your reply. Best wishes. , 
 Dear Dr. Biskrensis, We attach here the new version of Figure 4G, in which the mistake has been corrected. ![file] We alos corrected another mistake caused by figure arrangement when using Adobe illustrator. ![file] We have already apply to the editor of Cancer Cell internation to help us correct the misplaced pictures. Thanks so much again for pointing out these errors for us. Jie Bao ,