Downregulation of RPN2 induces apoptosis and inhibits migration and invasion in colon carcinoma

The morbidity of colorectal cancer (CRC) increases annualy, which accounts to higher mortality worldwide. Therefore, it is important to study the pathogenesis of colon cancer. Ribophorin II (RPN2), part of the N-oligosaccharyltransferase complex, is highly expressed in CRC. In the present study, we investigated whether RPN2 can regulate apoptosis, migration and invasion by RNA interference in CRC and sought to clarify the molecular mechanism involved. Based on previous research, an abnormal high expression of RPN2 was observed in CRC tissues and cell lines by real-time (RT)-PCR, immunohistochemistry (IHC) and western blot analysis. RPN2 knockdown via small RNA interference (siRNA) strategy attenuated the expression of RPN2 at the mRNA and protein levels in vivo, leading to decreased cell viability and increased cell apoptosis. In addition, RNAi-RPN2 effectively arrested the cell cycle at the G0/G1-phase in SW1116 and SW480 cells. Furthermore, the Transwell assay demonstrated that cell migration and invasion abilities were significantly inhibited after cell transfection with RPN2 interference plasmid. The apoptosis-related protein (caspase-3) expression was increased and the cell cycle-related protein (cyclin D1) expression was decreased in the siRNA-RPN2 group. RT-PCR and western blot analysis results indicated that migration- and invasion-related proteins including E-cadherin, matrix metalloproteinases (MMP)-2 and TIMP-2 were markedly regulated by RPN2 siRNA. Phosphorylation levels of signal transducer and activator of transcription (STAT)3 and Janus kinase (JAK)2 were inhibited by RPN2 siRNA. These findings indicated a novel pathway of tumor-promoting activity by RPN2 in CRC, with significant implications for unraveling the tumorigenesis of CRC.