Circ-RNF121 regulates tumor progression and glucose metabolism by miR-1224-5p/FOXM1 axis in colorectal cancer

Abstract

Abstract Aim Previous studies have reported that circular RNA (circRNA) is associated with the pathogenesis of CRC. This study was designed to reveal the mechanism of circ-ring finger protein 121 (circ-RNF121) in colorectal cancer (CRC). Materials and methods The levels of circ-RNF121, microRNA-1224-5p (miR-1224-5p) and forkhead box M1 (FOXM1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was detected by western blot. Cell proliferation was analyzed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. Flow cytometry analysis was performed to investigate cell apoptosis. Cell migration and invasion were investigated by transwell and wound-healing assays. Cell glycolysis was detected using glucose, lactate and ADP/ATP ratio assay kits. The binding relationship between miR-1224-5p and circ-RNF121 or FOXM1 was predicted by starBase online database, and identified by dual-luciferase reporter assay. The impacts of circ-RNF121 silencing on tumor formation in vivo were disclosed by in vivo tumor formation assay. Key findings Circ-RNF121 and FOXM1 expression were dramatically upregulated, while miR-1224-5p expression was downregulated in CRC tissues or cells compared with control groups. Circ-RNF121 silencing repressed cell proliferation, migration, invasion and glycolysis but induced cell apoptosis in CRC, which were attenuated by miR-1224-5p inhibitor. Additionally, circ-RNF121 acted as a sponge of miR-1224-5p and miR-1224-5p bound to FOXM1. Circ-RNF121 silencing inhibited tumor growth in vivo. Furthermore, circ-RNF121 was secreted through being packaged into exosomes. Significance The finding provided a novel insight into studying circRNA-mediated CRC therapy.