M6A-modified circARHGAP12 promotes the aerobic glycolysis of doxorubicin-resistance osteosarcoma by targeting c-Myc

Abstract

Chemotherapy resistance accompanied by energy metabolism abnormality functions as one of the main reasons for treatment failure and poor prognosis. However, the function of N6-methyladenosine (m6A)-modified circular RNA (circRNA) on osteosarcoma (OS) is still unclear. Here, present research investigated the potential role and mechanism of circARHGAP12 on OS doxorubicin (Dox) resistance and aerobic glycolysis. Results indicated that circARHGAP12 was a novel m6A-modified circRNA, which was up-regulated in OS cells. Overexpression of circARHGAP12 promoted the Dox resistance half-maximal inhibitory concentration (IC50) and aerobic glycolysis (glucose uptake, lactate and ATP production) in OS cells (Saos-2/Dox, MG63/Dox). Mechanistically, m6A-modified circARHGAP12 could bind with c-Myc mRNA through m6A-dependent manner, thereby enhancing the c-Myc mRNA stability. Thus, these findings revealed the critical function of circARHGAP12 on OS Dox-resistance and aerobic glycolysis. Taken together, our study demonstrated a critical function of circARHGAP12 on OS chemotherapy resistance and energy metabolism abnormality, providing critical roles on OS treatment.