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m6A-modified circFOXK2 targets GLUT1 to accelerate oral squamous cell carcinoma aerobic glycolysis


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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Fig. 1: m6A-circRNA microarray analysis revealed the m6A-modified circRNA in OSCC.
Fig. 2: circFOXK2 was a m6A-modified circRNA that upregulated in OSCC.
Fig. 3: circFOXK2 accelerated the malignant phenotype of OSCC.
Fig. 4: GLUT1 acted as the target of circFOXK2.
Fig. 5: circFOXK2 cooperated with IGF2BP3 to enhance GLUT1 mRNA stability.

Data availability

The m6A-circRNA microarray data from this publication have been deposited in NCBI’s Gene Expression Omnibus database and assigned the GEO Series accession number GSE198105. The MeRIP-Seq data are available in the NCBI Gene Expression Omnibus (GEO): accession number GSE197457.


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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).

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YC, JL, and LL performed the experiments. YG and XM act as the assists. WZ and HL are responsible for the designing and funding. All authors read and approved the final manuscript.

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Correspondence to Hao Liu or Wei Zhao.

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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).

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