Circ‐CTNNB1 drives aerobic glycolysis and osteosarcoma progression via m6A modification through interacting with RBM15

Abstract Objectives Circular RNAs (circRNAs) are a subclass of noncoding RNAs, playing essential roles in tumorigenesis and aggressiveness. Recent studies have revealed the pivotal functions of circ‐CTNNB1 (a circular RNA derived from CTNNB1) in cancer progression. However, little is known about the role of circ‐CTNNB1 in osteosarcoma (OS), a highly malignant bone tumour in children and adolescents. Methods Circ‐CTNNB1 was analysed by qRT‐PCR, and the results were confirmed by Sanger sequencing. The interaction and effects between circ‐CTNNB1 and RNA binding motif protein 15 (RBM15) were analysed through biotin‐labelled RNA pull‐down and mass spectrometry, in vitro binding, and RNA electrophoretic mobility shift assays. In vitro and in vivo experiments were performed to evaluate the biological functions and underlying mechanisms of circ‐CTNNB1 and RBM15 in OS cells. Results Circ‐CTNNB1 was highly expressed in OS tissues and predominantly detected in the nucleus of OS cells. Ectopic expression of circ‐CTNNB1 promoted the growth, invasion, and metastasis of OS cells in vitro and in vivo. Mechanistically, circ‐CTNNB1 interacted with RBM15 and subsequently promoted the expression of hexokinase 2 (HK2), glucose‐6‐phosphate isomerase (GPI) and phosphoglycerate kinase 1 (PGK1) through N6‐methyladenosine (m6A) modification to facilitate the glycolysis process and activate OS progression. Conclusions Circ‐CTNNB1 drives aerobic glycolysis and OS progression by facilitating RBM15‐mediated m6A modification.