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

Cancer Gene Therapy volume 30, pages 163–171 (2023)Cite this article

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Abstract

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.

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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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Funding

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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Author notes

  1. These authors contributed equally: Yameng Cui, Jingwen Liu, Lina Liu.

Authors and Affiliations

  1. Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, 300060, Tianjin, China

    Yameng Cui

  2. The School and Hospital of Stomatology, Tianjin Medical University, 300070, Tianjin, China

    Jingwen Liu, Xiaozhou Ma, Yu Gui & Wei Zhao

  3. Department of Prosthodontics, Tianjin Stomatological Hospital, Hospital of Stomatology, NanKai University, 300041, Tianjin, China

    Lina Liu & Hao Liu

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  1. Yameng Cui
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Contributions

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 30, 163–171 (2023). https://doi.org/10.1038/s41417-022-00526-6

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