N6-methyladenosine (m6A) is an abundant nucleotide modification in mRNA, and its emerging roles have been gradually identified. However, the potential function of m6A and m6A-modified circular RNA (circRNA) is still unclear. Here, m6A-circRNA epitranscriptomic microarray analysis revealed a high-expressed m6A-modified circFOXK2 (hsa_circ_0000816, from FOXK2 gene) in oral squamous cell carcinoma (OSCC). For the biofunctions of OSCC, results revealed that circFOXK2 promoted the malignant phenotypes of OSCC cells. Methylated RNA immunoprecipitation sequencing (MeRIP-Seq) demonstrated that a remarkable m6A modified site was installed on glucose transporter 1 (GLUT1) mRNA. Mechanistically, circFOXK2 promoted the GLUT1 mRNA stability through cooperating with insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) in a m6A-dependent manner. In summary, the present study explored the oncogenic role of m6A-modified circFOXK2 in OSCC through the m6A-dependent IGF2BP3/GLUT1 axis, indicating a potential therapeutic target for OSCC.
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This work was supported by National Natural Science Foundation of China (No. 82002889, 82104631), Tianjin Medical University Stomatological Hospital Foundation (No: 2020YKY01), Project of integrated traditional Chinese and Western Medicine of Tianjin Health Commission (2021075), Hospital Project of Tianjin Medical University Cancer Institute and Hospital (No: B1908).
The authors declare no competing interests.
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Cui, Y., Liu, J., Liu, L. et al. m6A-modified circFOXK2 targets GLUT1 to accelerate oral squamous cell carcinoma aerobic glycolysis. Cancer Gene Ther (2022). https://doi.org/10.1038/s41417-022-00526-6