CircPCSK5 is highly expressed in gastric cancer and promotes cancer cell proliferation, invasion and epithelial-mesenchymal transition

Abstract

To investigate the expression of circPCSK5 in gastric cancer (GC) and its role in regulation of the proliferation, invasion and epithelial-mesenchymal transition (EMT) of GC cells. High-throughput sequencing was performed in 3 pairs of GC and adjacent gastric mucosa tissues to obtain the differential expression profile of circRNA. The expression of circPCSK5 was detected in 62 patients undergoing radical surgery for GC using RT-qPCR, and the correlation between circPCSK5 expression level and clinicopathological data of the patients was analyzed. The overall survival and disease-free survival of the patients were assessed with Kaplan-Meier survival analysis, and the independent risk factors affecting the patients' prognosis were analyzed using Cox proportional hazards regression model. The stability and subcellular localization of circPCSK5 were assessed using RNase R and actinomycin D assays, fluorescence in situ hybridization and nucleocytoplasmic separation assay. CCK-8 assay, EdU assay and Transwell assay were employed to examine the changes in proliferation, migration and invasion of GC cells with circPCSK5 knockdown or overexpression; Western blotting and RT-qPCR assays were used to detect the expression levels of EMT markers in the transfected cells. The expression of circPCSK5 was significantly upregulated in GC tissues and cells (P < 0.001, P < 0.01). The expression level of circPCSK5 was positively correlated with tumor size, vascular invasion, lymph node metastasis and AJCC stage of GC (P < 0.05). The overall survival and disease-free survival were significantly lower in GC patients with high circPCSK5 expression than in those with low circPCSK5 expression (P < 0.001). High circPCSK5 expression was an independent risk factor for a poor prognosis of GC patients (P < 0.05). Knockdown of circPCSK5 significantly inhibited the proliferation, migration and invasion of HGC27 cells (P < 0.01), increased the expressions of E-cadherin, and decreased the expression of N-cadherin and vimentin (P < 0.01). CircPCSK5 overexpression promoted the proliferation, migration and invasion of MKN45 cells (P < 0.01), reduced E-cadherin expression and increased N-cadherin and vimentin expressions (P < 0.01). CircPCSK5 is highly expressed in GC and promotes the proliferation, invasion and EMT of GC cells, suggesting its potential as a prognostic biomarker and therapeutic target for GC.