文章：

m6A修饰的circFOXK2靶向GLUT1促进口腔鳞状细胞癌的有氧糖酵解

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

原文发布日期：2022-09-20 

英文摘要：

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. 

摘要翻译： 

N6-甲基腺苷（m6A）是信使RNA中一种常见的核苷酸修饰，其新功能正逐渐被揭示。然而，m6A及m6A修饰的环状RNA（circRNA）的潜在作用仍不明确。本研究通过m6A-circRNA表观转录组芯片分析发现，m6A修饰的circFOXK2（hsa_circ_0000816，源自FOXK2基因）在口腔鳞状细胞癌（OSCC）中高表达。功能实验表明，circFOXK2能促进OSCC细胞的恶性表型。甲基化RNA免疫沉淀测序（MeRIP-Seq）显示葡萄糖转运蛋白1（GLUT1）mRNA上存在显著的m6A修饰位点。机制上，circFOXK2通过以m6A依赖的方式与胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）协同作用，增强GLUT1 mRNA的稳定性。本研究揭示了m6A修饰的circFOXK2通过m6A依赖的IGF2BP3/GLUT1轴在OSCC中发挥致癌作用，为OSCC提供了潜在的治疗靶点。

原文链接：

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