RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways

Abstract

This study aimed to investigate the function and the molecular mechanism of Ribophorin II (RPN2) in regulating Hepatocellular carcinoma (HCC) cell growth, metastasis, and autophagy. Quantitative real-time PCR (qPCR), western blotting analysis, and immunofluorescence assay were utilized to detect the RPN2 expression in HCC cell lines and specimens of HCC patients. We discovered that RPN2 expression was upregulated in HCC cell lines and tissues of HCC patients, which correlated with the low histological grade and low survival rate. Enhanced RPN2 expression stimulated cell proliferation, metastasis, invasion, and epithelial-mesenchymal transition (EMT), and decreased Microtubule-associated protein light chain 3B (LC3B) synthesis and reduced the expression of p62 protein. Further studies suggested that matrix metalloproteinase 9 (MMP-9) was partially upregulated by RPN2 via Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65. Interestingly, we found that phosphorylated RPN2 activated the signal transducer and activator of transcription 3 (STAT3) in HCC cells. It was also accountable for RPN2-stimulated elevated expression of MMP-9 and for invading HCC cells. It can be concluded that over-expression of RPN2 in HCC aggravated the malignant progression into cancerous cells. This research provided new evidences that RPN2 could facilitate tumor invasion by increasing the expression of MMP-9 in HCC cells.