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

Abstract

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.

The N6-methyladenosine-mediated lncRNA WEE2-AS1 promotes glioblastoma progression by stabilizing RPN2

“…Functional enrichment analysis showed that GBM samples with high expression of both WEE2-AS1 and RPN2 were significantly enriched in the AKT signaling pathway (Figure 4 A-C and Figure S1 ). In addition, PI3K-Akt was a downstream signaling pathway of RPN2 in other tumors articles 24 , 25 . Thus, we then investigated the phosphorylation levels of PI3K and Akt in WEE2-AS1 knockdown and overexpression GBM.…”

POLR3G promotes EMT via PI3K/AKT signaling pathway in bladder cancer

“…In BLCA, TEAD4 activates the PI3K/AKT pathway, which in turn promotes invasion and metastasis 27 . Knockdown of RPN2 gene has been shown to suppress EMT and inhibit the PI3K/AKT pathway 49 . Additionally, the E3 ubiquitin ligase RNF126 plays a key role in BLCA metastasis by regulating the stability of PTEN, an inhibitor of the PI3K/AKT signaling pathway 50 .…”

A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours

“…Additionally, we also identified 11 genes that interacted with HSP90B1 and were highly correlated with HSP90B1: RPN2, SDF2L1, HSPA5, HYOU1, PPIB, GANAB, PDIA6, PDIA4, CALR, TG, and P4HB. RPN2 is speculated to be involved in the progression of malignant tumours by regulating various signalling pathways, such as STAT3, NF-κB, and PI3K-Akt [ 40 , 41 ]. It is also considered a promising prognostic biomarker for colorectal cancer, non-small-cell lung cancer, and gastric adenocarcinoma [ 42 , 43 , 44 ].…”