Targeting CircAURKA prevents colorectal cancer progression via enhancing CTNNB1 protein degradation

Abstract

Tumor progression of colorectal cancer (CRC) seriously affects patient prognosis. For CRC patients with advanced-stage disease, it is still necessary to continuously explore more effective targeted therapeutic drugs. Circular RNAs (circRNAs) are involved in the regulation of tumor biology. We screened circAURKA, which was significantly highly expressed in CRC by previous high-throughput RNA sequencing. In vitro experiments were performed to investigate the effect of the circRNA on the proliferation and metastasis of HCT116 and SW480 cells. In addition, we used the EdU assay, Transwell assay, nude mouse xenograft tumor model and nude mouse tail vein metastasis model to examine the effect of circAURKA on the proliferation and metastasis of CRC. Mechanistically, fluorescent in situ hybridization (FISH), RNA pull-down, RNA immunoprecipitation (RIP), protein coimmunoprecipitation (co-IP) experiments and animal models were performed to confirm the underlying mechanisms of circAURKA. CircAURKA was significantly highly expressed in CRC tissues and colorectal cells and mainly present in the cytoplasm. The circRNA promoted the proliferation and metastasis of CRC cells in vitro and in vivo. In terms of the molecular mechanism, circAURKA inhibited the degradation of the CTNNB1 protein by promoting the interaction between ACLY and the CTNNB1 protein, thereby promoting the proliferation and metastasis of CRC cells. In addition, circAURKA stability was regulated by m6A methylation modification. This study revealed that circAURKA promoted the proliferation and metastasis of CRC by inhibiting CTNNB1 protein degradation, providing a basis for the development of targeted drugs to control CRC progression.