Copine 8 promotes proliferation, invasion and metastasis of pancreatic cancer

Abstract

Objective To explore the biological role of copine 8 in the occurrence and progression of pancreatic cancer. Methods GEO datasets were used to compare the expression of copine 8 in pancreatic cancer tissues and adjacent tissues, and TCGA datasets were used to analyze the impact of copine 8 expression on the patients' overall survival rate. The differentially expressed genes between the patients with high and low copine 8 expression were analyzed using GO, KEGG enrichment analysis and gene set enrichment analysis (GSEA). The effect of small interfering RNA-mediated silencing of copine 8 on proliferation, invasion, metastasis, and apoptosis of pancreatic cancer cell lines CFPAC-1 and AsPC-1 were examined using CCK8 assay, colony formation assay, transwell assay, and Annexin V-FITC and propidium iodide staining. The pancreatic cancer transcriptome dataset was analyzed to identify the pathways regulated by copine 8. Results Copine 8 mRNA and protein were highly expressed in pancreatic cancer tissues and lowly expressed in adjacent tissues. Copine 8 expression was significantly correlated with the survival prognosis of the patients with pancreatic cancer (P=0.033). Enrichment analysis showed that copine 8 affected WNT, Hippo, mTOR, and ERBB signaling pathways in pancreatic cancer, and may promote the progression of pancreatic cancer by affecting the expression of the key molecules YAP1, STK3, STK4 and SGMS1 in Hippo pathway. Interference of copine 8 expression significantly suppressed the proliferation, invasion and migration and obviously increased the number of apoptotic cells in 2 pancreatic cancer cell lines. Conclusion Copine 8 has a strong cancer-promoting effect and plays a significant role in the proliferation, invasion, metastasis and apoptosis of pancreatic cancer.

Keywords

• copine 8
• pancreatic cancer
• proliferation
• apoptosis
• invasion and metastasis