METTL3通过调节COL4A1的甲基化水平参与胶质瘤的发展。
METTL3 participates in glioma development by regulating the methylation level of COL4A1.
作者信息
Han Jianguo, Du Shiwei, Wu Chong, Qiu Ming, Su Li, Zhao Zhijun, Cheng Si, Tao Wei
机构信息
Department of Neurosurgery, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy Centre, Shenzhen University, Shenzhen, China.
出版信息
J BUON. 2021 Jul-Aug;26(4):1556-1562.
PURPOSE
The role of RNA methylation in human cancers has emerged. Its biological function in glioma development is explored in the present study.
METHODS
Differential levels and prognostic potentials of COL4A1 and METTL3 in glioma were analyzed by bioinformatic method. The regulatory effect of METTL3 on COL4A1 was assessed through qRT-PCR, MeRIP and dual-luciferase reporter assay. Their biological functions in influencing proliferative and metastatic capacities of glioma cells were examined by EdU, colony formation and Transwell assay, respectively.
RESULTS
COL4A1 was upregulated in glioma tissues, and METTL3 was downregulated. Knockdown of METTL3 in U87 and U251 cells could reduce the methylation level of COL4A1 and upregulate its expression level. Intervention of COL4A1 suppressed proliferative and metastatic capacities of glioma cells, while intervention of METTL3 yielded the opposite results.
CONCLUSION
METTL3 reduces the methylation level of COL4A1 and upregulates its expression level, which further stimulates the malignant development of glioma. METTL3/COL4A1 can be potential therapeutic targets of glioma.
目的
RNA甲基化在人类癌症中的作用已逐渐显现。本研究旨在探讨其在胶质瘤发生发展中的生物学功能。
方法
采用生物信息学方法分析胶质瘤中COL4A1和METTL3的差异表达水平及预后潜力。通过qRT-PCR、MeRIP和双荧光素酶报告基因检测评估METTL3对COL4A1的调控作用。分别采用EdU、集落形成实验和Transwell实验检测它们对胶质瘤细胞增殖和转移能力的生物学功能影响。
结果
COL4A1在胶质瘤组织中上调，而METTL3下调。在U87和U251细胞中敲低METTL3可降低COL4A1的甲基化水平并上调其表达水平。干预COL4A1可抑制胶质瘤细胞的增殖和转移能力，而干预METTL3则产生相反结果。
结论
METTL3降低COL4A1的甲基化水平并上调其表达水平，进而促进胶质瘤的恶性发展。METTL3/COL4A1可能成为胶质瘤的潜在治疗靶点。
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