Various studies have found that silencing ribophorin II (RPN2) inhibits cell growth in several cancers. However, the underlying mechanism by which RPN2 regulates cancer cell proliferation remains unclear. Herein, we reveal that downregulation of RPN2, which may be a crucial regulator of N-linked glycosylation in cancer cells and drug-resistant cancer cells, promoted the progression of colorectal cancer (CRC) cell cycle and proliferation in vitro and in vivo. We found that RPN2 silencing reduced glycosylation of EGFR, a highly N-link glycosylated cell surface glycoprotein that plays a critical role in majority of human cancers correlating with increased cell growth, proliferation, and differentiation. In addition, RPN2 knockdown decreased EGFR expression and cell surface transport by EGFR deglycosylation. In summary, our findings suggest that RPN2 regulates CRC cell proliferation through mediating the glycosylation of EGFR which affecting the EGFR/ERK signaling pathways. Clinicopathological analysis showed that the overexpression of RPN2 and EGFR was positively correlated with colorectal tumor size. Therefore, RPN2 may be a new therapeutic target and prognostic biomarker for CRC.
Keywords: EGFR; RPN2; colorectal cancer; glycosylation; proliferation.