Circular RNA UBR1 promotes the proliferation, migration, and invasion but represses apoptosis of lung cancer cells via modulating microRNA-545-5p/SSFA2 axis

Abstract

ABSTRACT Lung cancer (LC) is a malignant tumor with the highest incidence in the world, and its specific pathogenesis is still unclear. Circular RNAs (circRNAs) are a group of non-coding RNAs that play a key role in the development and progression of various cancers. The expression pattern and function of circRNAs in LC are still not completely distinct. In this study, it was aimed to study the expression and potential mechanism of circ-UBR1 in LC cells. Then it was found that circ-UBR1 was up-regulated in LC cells, and had microRNA (miR)-545-5p binding sites. Meanwhile, it was confirmed by dual-luciferase reporter assay that circ-UBR1 directly bound to miR-545-5p and then repressed its expression. MiR-545-5p was down-regulated in LC cells and refrained its expression by binding to the downstream target gene SSFA2. Knockdown circ-UBR1 or enhancive miR-545-5p repressed A549 cell proliferation, migration, and invasion, but accelerated apoptosis. After transfection with circ-UBR1 low expression vector, upregulation of SSFA2 apparently reversed the depression of reduced circ-UBR1 on cell proliferation, migration, and invasion, and the promotion of cell apoptosis. Further tumor xenograft experiments in nude mice also confirmed that knockdown of circ-UBR1 could increase the expression of miR-545-5p, but decrease the expression of SSFA2, thus alleviating the progression of LC in vivo. Therefore, these results fully indicate that circ-UBR1 promotes LC cell proliferation, migration, and invasion, but represses apoptosis via the circ-UBR1 axis, which may be a closely related marker and therapeutic target of LC.