miR-4792通过结合BACE1调节胰腺癌增殖、迁移和侵袭

目的 探究miR-4792对胰腺癌增殖、 迁移和侵袭的影响.方法 下载GSE59856和GSE71533数据集,取上调表达的交集基因miR-4792,构建稳定过表达miR-4792的胰腺癌细胞系PANC-1、SW1990,采用CCK-8实验和Transwell小室实验检测细胞增殖、 迁移和侵袭能力,通过裸鼠皮下种植瘤模...

mir-4792 Regulates the Proliferation,Migration and Invasion of Pan-creatic Cancer by Targeting BACE1

Objective To explore the effects of miR-4792 on the proliferation, migration andinvasion of pancreatic cancer. Methods GSE59856 and GSE71533 data sets were downloaded. Theintersection of the up-regulated genes in the two data sets was the gene miR-4792. Pancreatic cancercell lines PANC-1 and SW1990, which could overexpress miR-4792, were then constructed. Thecell proliferation was measured by CCK-8. Cell migration and invasion were measured by transwellchamber 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 targetBACE1 was verified. Results In the miR-4792 group relative to the miR-NC group, the miR-4792level, the cell proliferation ability and the number of migratory and invasive cells were significantlyincreased. The tumor volume was significantly enhanced in miR-4792 group compared with miR-NCgroup. The volume and weight of the tumor, and the miR-4792 expression level were significantlyincreased in the miR-4792 group (P< 0. 05). It was predicted by Targetscan that the target gene ofmiR-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 wasconfirmed by dual luciferase reporter gene assay that miR-4792 could directly act on the 3′UTR ofBACE1 to down-regulate its expression. Compared with the miR-NC group, the expression levels ofBACE1 mRNA and protein were decreased in the miR-4792 group (P< 0. 05). The expression levelof BACE1 protein was significantly increased, and the cell proliferation ability and the number ofmigration and invasion cells were significantly decreased in the miR-4792 + BACE1 group comparedwith the miR-4792 group (P < 0. 05). However, the differences of the above indexes between themiR-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 bethrough the down-regulation of its target gene BACE1.