m 6 A-modified circFOXK2 targets GLUT1 to accelerate oral squamous cell carcinoma aerobic glycolysis

Cancer Gene Therapy(2022)

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摘要
N 6 -methyladenosine (m 6 A) is an abundant nucleotide modification in mRNA, and its emerging roles have been gradually identified. However, the potential function of m 6 A and m 6 A-modified circular RNA (circRNA) is still unclear. Here, m 6 A-circRNA epitranscriptomic microarray analysis revealed a high-expressed m 6 A-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 m 6 A 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 m 6 A-dependent manner. In summary, the present study explored the oncogenic role of m 6 A-modified circFOXK2 in OSCC through the m 6 A-dependent IGF2BP3/GLUT1 axis, indicating a potential therapeutic target for OSCC.
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关键词
oral squamous cell carcinoma,glut1,squamous cell carcinoma,a-modified
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