关键词: 胰腺癌, miR-4792, β-淀粉样前体蛋白裂解酶 1, 增殖, 迁移, 侵袭

Abstract: Objective To explore the effects of miR-4792 on the proliferation, migration and invasion of pancreatic cancer. Methods GSE59856 and GSE71533 data sets were downloaded. The intersection of the up-regulated genes in the two data sets was the gene miR-4792. Pancreatic cancer cell lines PANC-1 and SW1990, which could overexpress miR-4792, were then constructed. The cell proliferation was measured by CCK-8. Cell migration and invasion were measured by transwell chamber assay. The effects of miR-4792 overexpression on tumor growth were determined by the subcutaneous xenograft model of nude mice. The target genes of miR-4792 were predicted by Targetscan. GSE62452 and TCGA data sets were downloaded to screen out the gene beta-site APP cleaving enzyme-1 (BACE1). The relationship between the BACE1 expression and the clinical phenotypes of malignant pancreatic cancer was analyzed. The relationship between miR-4792 and its target BACE1 was verified. Results In the miR-4792 group relative to the miR-NC group, the miR-4792 level, the cell proliferation ability and the number of migratory and invasive cells were significantly increased. The tumor volume was significantly enhanced in miR-4792 group compared with miR-NC group. The volume and weight of the tumor, and the miR-4792 expression level were significantly increased in the miR-4792 group (P< 0. 05). It was predicted by Targetscan that the target gene of miR-4792 was BACE1, whose expression was closely related to the recurrence, proliferation, progression-free survival, prognosis, M staging and G staging of pancreatic cancer (P< 0. 05). It was confirmed by dual luciferase reporter gene assay that miR-4792 could directly act on the 3′UTR of BACE1 to down-regulate its expression. Compared with the miR-NC group, the expression levels of BACE1 mRNA and protein were decreased in the miR-4792 group (P< 0. 05). The expression level of BACE1 protein was significantly increased, and the cell proliferation ability and the number of migration and invasion cells were significantly decreased in the miR-4792 + BACE1 group compared with the miR-4792 group (P < 0. 05). However, the differences of the above indexes between the miR-4792 + BACE1 group and the miR-NC group were not statistically significant ( P > 0. 05). Conclusion The expression of miR-4792 is up-regulated in pancreatic cancer, and its overexpression can promote the proliferation, migration and invasion of pancreatic cancer cells, which may be through the down-regulation of its target gene BACE1.

Key words: pancreatic cancer, miR-4792, beta-site APP cleaving enzyme-1, proliferation, migration, invasion