Abstract
Background: Ribophorin family (RPNs) are important regulatory subunits of the proteasome. By influencing Ubiquitin-proteasome system activity, RPNs are responsible for almost all processes of physiology and pathology of mammalian cells. Nevertheless, little is known about the role of RPNs in HCC.Methods: In this work, using the online databases Oncomine, UCSC, Kaplan-Meier Plotter, UALCAN, cBioPortal, TIMER2, GeneMANIA,and STRING, we first evaluated the expression, diagnostic, prognostic, genetic alteration, immunity, gene network, and functional enrichment of RPNs in HCC. QPCR and western blot were used to detect RPN6 and RPN9 expressions in HCC tissues and cell lines. Then we performed studies to eveulated their functions in HCC cells proliferation, migration, and invasion in vitro. Results: All RPNs were surprisingly consistently upregulated in HCC tissues. Moreover, RPNs expression pattern is correlated with HCC tumor grade. RPN2, RPN3, RPN6, RPN9, RPN10, RPN11, and RPN12 have robust values in HCC diagnose. Then, survival analysis revealed that high expression of RPN1, RPN2, RPN4, RPN5, RPN6, RPN9, and RPN11were correlated with unfavorable HCC overall survival. Functional enrichment for RPNs, indicated that RPNs have many potential biosynthesis activities expert for UPS functions. Western blot, and qRT-PCR further verified these results in HCC tissues and cell lines. The silencing of RPN6 and RPN9 significantly influenced HCC cells' proliferation, migration, and invasion in vitro.Conclusions: RPN families functions as an important oncogene in HCC. RPN6 and RPN9 have the potential to be potential biomarkers and targets for HCC.