RPNs Levels Are Prognostic and Diagnostic Markers for Hepatocellular Carcinoma

Abstract

The ribophorin family (RPN) is an essential regulatory subunit of the proteasome. By influencing the ubiquitin-proteasome system activity, ribophorins (RPNs) are responsible for almost all physiology and pathology processes of mammalian cells. Nevertheless, little is known about the role of RPNs in HCC. In this work, we first evaluated the transcriptional levels and the prognostic and diagnostic value of RPNs based on the public database. Firstly, we found all RPNs were surprisingly consistently upregulated in HCC tissues. Moreover, the RPNs’ expression pattern is correlated with HCC tumor grade. The TCGA HCC platforms’ data indicated that RPN2, RPN3, RPN6, RPN9, RPN10, RPN11, and RPN12 have robust diagnosis values. Then, survival analysis revealed that the high expression of RPN1, RPN2, RPN4, RPN5, RPN6, RPN9, and RPN11 was correlated with unfavourable HCC overall survival. Then, genetic alteration, immune infiltration feature, gene-genes network, and functional enrichment for RPNs indicated that RPNs have many potential biosynthesis activities expert for UPS functions. Moreover, western blot and qRT-PCR results confirmed these results. The silencing of RPN6 and RPN9 significantly reduced HCC cells’ proliferation, migration, and invasion ability in vitro. An in vivo tumor model further validated the oncogene effect of RPN6 on HCC cell growth. Moreover, RPN6 and RPN9 could promote cell migratory and invasive potential by affecting the epithelial-mesenchymal transition (EMT) process. In summary, this study suggests that the RPN family has the potential to be potential biomarkers and targets for HCC.

Pan-cancer analysis of the disulfidptosis-related gene RPN1 and its potential biological function and prognostic significance in gliomas

“…Several studies have shown that disulfidptosis-related genes (DRGs) are involved in the development and progression of various cancers [ 36 ]. The ribonucleoprotein (RPN) family is an essential regulatory subunit of the proteasome that affects cellular physiological and pathological processes by regulating proteasome activity, leading to tumorigenesis [ 37 , 38 ]. RPN1 , a critical gene in the RPN family associated with disulfidptosis, was investigated for its potential impact on cancer.…”

RPN1: a pan-cancer biomarker and disulfidptosis regulator

“…For instance, RPN1 promotes proliferation, migration, and invasion of breast cancer cells through the PI3K / AKT / mTOR signaling pathway ( 8 ), possibly by inhibiting apoptosis triggered by endoplasmic reticulum stress ( 17 ). In HCC, survival analysis shows that high RPN1 expression is associated with adverse OS in HCC patients ( 9 ). Zheng et al found that the Circ-SNX27 sponging miR-375/ RPN1 axis contributes to HCC progression ( 18 ).…”

“…Several studies have investigated the relationship between RPN1 and cancer. For example, it may promote the progression of breast cancer ( 8 ) and be associated with poor prognosis in hepatocellular carcinoma (HCC) ( 9 ). However, the biomarker value of RPN1 across pan-cancers has yet to be investigated.…”

Disulfidptosis-related signature to guide the prognosis prediction and treatment in hepatocellular carcinoma

“…Our ndings are supported by certain experimental and bioinformatics studies. [25][26][27][28][29][30][31][32] Nevertheless, the expression and prognosis of BRK1 in HCC have not been investigated. Then based on DRS, two subgroups were identi ed, HDS-group and LDS-group.…”