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RPN2 Predicts Poor Prognosis and Promotes Bladder Cancer Growth and Metastasis via the PI3K-Akt Pathway

Authors Han C, Chen S, Ma H, Wen X, Wang Z, Xu Y, Jin X, Yu X, Wang M

Received 8 January 2021

Accepted for publication 20 February 2021

Published 3 March 2021 Volume 2021:14 Pages 1643—1657

DOI https://doi.org/10.2147/OTT.S300480

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Professor Gaetano Romano


Chenglin Han,1 Shuxiao Chen,2 Haiyang Ma,3 Xiangchuan Wen,4 Zilong Wang,1 Yingkun Xu,1 Xunbo Jin,1,5 Xiao Yu,5 Muwen Wang1,5

1Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Vascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Thoracic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 5Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China

Correspondence: Xiao Yu
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road, Huaiyin District, Jinan City, Shandong Province, People’s Republic of China
Tel +86-15168889682
Email [email protected]
Muwen Wang
Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, 9677 Jingshidong Road, Jinan City, Shandong Province, People’s Republic of China
Tel +86-15168886899
Email [email protected]

Background: Ribophorin II (RPN2) is a highly conserved glycoprotein involved in the N-linked glycosylation of multiple proteins. RPN2 was reported to be associated with malignant phenotype in several tumors. However, the function of RPN2 in bladder cancer (BCa) remains unclear.
Methods: Expression of RPN2 in BCa and adjacent tissues was compared by bioinformatics analysis, immunohistochemistry, and Western blotting. qRT-PCR was performed to explore the correlation between RPN2 expression and various clinical features in 38 patients. We assessed the effects of RPN2 on the biological activity of BCa both in vitro and in vivo, and explored its potential mechanisms based on gene set enrichment analysis (GSEA).
Results: We found that RPN2 was highly expressed in human BCa compared with normal adjacent tissues. There was a significant positive correlation between higher RPN2 mRNA levels and tumor T stage, lymph node (LN) metastasis and the degree of pathological differentiation in 38 patients with BCa. We further demonstrated that RPN2 silencing inhibited the growth and metastasis of BCa both in vitro and in vivo. Western blotting revealed that RPN2 knockdown suppressed epithelial-mesenchymal transition (EMT) and inhibited the PI3K-Akt pathway.
Conclusion: These data suggest that RPN2 functions as an oncogene to promote tumor development and is a promising prognostic factor and therapeutic target in BCa.

Keywords: bladder cancer, RPN2, poor prognosis, EMT, PI3K-Akt pathway

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