m6A-modified circASXL1 promotes proliferation and migration of ovarian cancer through the miR-320d/RACGAP1 axis

Abstract

Ovarian cancer (OC) is one of the most common malignant tumors in women. Circular RNAs (circRNAs) can potentially regulate the development of OC. Therefore, this study investigated the role of circASXL1 in OC progression. Cell functions were assessed by MTT, colony formation, wound healing, and transwell assays. RIP and dual luciferase reporter assays confirmed the relationship between miR-320d and circASXL1 or RACGAP1. MeRIP was utilized to detect m6A levels. Xenograft tumor was established for in vivo experiments. CircASXL1 and RACGAP1 levels were increased in OC tissues and cells, whereas miR-320d expression was decreased. Upregulation of circASXL1 was associated with poor prognosis in OC patients. CircASXL1 silencing suppressed OC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, METTL3/IGF2BP1-mediated m6A modification maintained circASXL1 stability and upregulated its expression. CircASXL1 was a ceRNA that sequestrated miR-320d from RACGAP1, leading to increased RACGAP1 expression. CircASXL1 promoted OC cell proliferation, migration and invasion via the miR-320d/RACGAP1 axis. Therefore, m6A-modified circASXL1 acts as an oncogene in OC by targeting miR-320d and activating RACGAP1/PI3K/Akt pathway, which provides novel promising biomarkers for OC diagnosis.