A Low Level of CircPVRL3 Promotes Pancreatic Cancer Proliferation and Metastasis Through miR-194-5p/SOCS2 Axis

Abstract

INTRODUCTION: The circular RNAs play essential roles for different types of cancer via sponging miRNAs. In the present study, we investigated that a low level of circPVRL3 promotes the processes of proliferation and metastasis in pancreatic ductal adenocarcinoma (PDAC) through miR-194-5p/SOCS2 axis. METHODS: Tumor samples from 56 cases PDAC patients were observed. A total of 22 (39.3%) cases were positive (high expression), and 34 (60.7%) were negative. The mechanism of proliferation and metastasis carried by miR-194-5p in PDAC cells was observed. Upstream gene circPVRL3 and downstream target gene SOCS2 of miR-194-5p were investigated by bioinformatic methods and mRNA-seq evaluation. Nude mice underwent subcutaneously injected PDAC cells and were treated with/without miR-194-5p agomir/antagomir to observe tumor weight and size. RESULTS: Tissue microarray test showed that the expression of miR-194-5p was higher in PDAC tissue than in tumor-adjacent tissue, and miR-194-5p expression was positively correlated with age (p = 0.028) and neuroinvasion (p = 0.021). CircPVRL3, SOCS2, and miR-194-5p were confirmed that constituted competing endogenous RNAs. Overexpression of miR-194-5p targeted SOCS2 promoted the progression of PDAC via regulating cell cycle and migration. Knockdown expression of circPVRL3 showed the same effects on PDAC cells. Animal experiments showed overexpression of miR-194-5p has a proliferation-promoted effect on tumor weight and size (Figure).FigureCONCLUSION: The present study revealed that low expression of circPVRL3 contributes to reducing the expression of SOCS2 through releasing for miR-194-5p in excess, which promoted proliferation and metastasis of PDAC. The unexpected result was that this phenomenon might be through phosphorylation of AKT that would be further studied.