m<sup>6</sup>A-modified circARHGAP12 promotes the aerobic glycolysis of doxorubicin-resistance osteosarcoma by targeting c-Myc.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38178201.
- Also identified by DOI 10.1186/s13018-023-04502-0 and PMC identifier 10768094.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 N<sup>6</sup>-methyladenosine (m<sup>6</sup>A)-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 m<sup>6</sup>A-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, m<sup>6</sup>A-modified circARHGAP12 could bind with c-Myc mRNA through m<sup>6</sup>A-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.
Medical subject headings
- Osteosarcoma
- Bone Neoplasms