circPUM1 Activates the PI3K/AKT Signaling Pathway by Sponging to Promote the Proliferation, Invasion and Glycolysis of Pancreatic Cancer

Abstract

Background: Our study seeks to obtain data to assess the impact of circPUM1 on pancreatic cancer (PC) and its mechanism.

Methods: The expression of circPUM1 and miR-200c-3p in PC and normal tissues and PC cell lines was collected and detected, and subsequently dual-luciferase assay-based verification of the binding site of the two was carried out. After interfering with circPUM1 expression in MIAPaCa-2 and PANC-1 cells, cell proliferation, viability, apoptosis rate, invasion ability, glucose consumption, and lactate production were measured by MTT, colony formation, flow cytometry, Transwell assays, and glucose and lactate assay kits. Additionally, western blot was utilized for assessing PI3K/AKT signaling pathway-related proteins. From the results, highly expressed circPUM1 and miR-200c-3p in PC tissues and cells were proved.

Results: Down-regulation of circPUM1 expression significantly inhibited cell proliferation, cell viability, invasion and glycolysis, while increasing the apoptosis rate. Down-regulated circPUM1 led to the inhibition of the PI3K/AKT signaling pathway activity in PC cells; while up-regulated circPUM1 increased its activity. Further experiments revealed that down-regulation of miR-200c-3p expression reversed the inhibitory effect of lowly expressed circPUM1 on PC cells.

Conclusion: In summary, circPUM1 activates PI3K/AKT signaling pathway by sponging miR-200c-3p and promotes PC progression.

Keywords: Pancreatic cancer; circPUM1; dual-luciferase assay; flow cytometry; miR-200c-3p; molecular sponge.