CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1

Abstract

AbstractColorectal cancer (CRC) is a common malignancy with high occurrence and mortality worldwide. In recent years, the overall survival rate of CRC patients has been improved because of the advances in early diagnosis and therapy. However, the prognosis of CRC patients at the advanced stage is still poor due to high recurrence rate and metastasis. The function of circular RNA (circRNA) ArfGAP with FG repeats 1 (circAGFG1) has been explored in non-small-cell lung cancer and triple-negative breast cancer. Nevertheless, its role in CRC is not clear. In this study, circAGFG1 was upregulated in CRC cell lines. CircAGFG1 silencing significantly suppressed cell proliferation, migration, invasion, and stemness, while promoted cell apoptosis in CRC. Meanwhile, we found that circAGFG1 also accelerated CRC tumor growth and metastasis in vivo. Importantly, circAGFG1 activated Wnt/β-catenin pathway through regulating CTNNB1. Afterwards, YY1 was found to transcriptionally activate CTNNB1. Furthermore, circAGFG1 directly sponged miR-4262 and miR-185-5p to upregulate YY1 expression. Eventually, rescue assays demonstrated that the effect of circAGFG1 silencing on CRC cell functions was observably reversed by upregulating YY1 or CTNNB1. In brief, our findings uncovered that circAGFG1 modulated YY1/CTNNB1 axis to drive metastasis and stemness in CRC by sponging miR-4262 and miR-185-5p.