文章：

METTL3通过N6-甲基腺苷修饰SFRP2促进非小细胞肺癌的恶性进展

METTL3 promotes the malignancy of non-small cell lung cancer by N6-methyladenosine modifying SFRP2 

原文发布日期：2023-04-27 

英文摘要：

This study aimed to investigate the roles of METTL3, a regulator of m6A, in NSCLC. RT-qPCR was applied to determine mRNA of m6A-associated genes and SFRP2, and western blot were used for ZEB1 and MMP9 protein expression. Total m6A level was measured using methylated RNA immunoprecipitation (MeRIP) assay, and RIP was used to access m6A level of SFRP2. Cellular behaviors were detected using CCK-8 and tranwell assays. Xenograft assays were conducted to further verify the roles of METTL3 and SFRP2 in NSCLC. The expression level of METTL3 was higher in NSCLC than normal controls. However, downregulation of METTL3 restrained the proliferation, migration and invasion of NSCLC cells. Enhanced expression of METTL3 caused the inverse consequences. Moreover, SFRP2 was found to be negatively regulated by METTL3. Intriguingly, the anti-tumor functions of METTL3 knockdown in the phenotype of NSCLC cells and xenograft mice were overturned by inhibition of SFRP2. Silencing METTL3 resulted in the enhanced stability of SFRP2. Finally, downregulation of SFRP2 induced by METTL3 activated the Wnt/β-catenin signaling pathway in NSCLC. METTL3 acted as an oncogene in the pathogenesis of NSCLC via suppressing SFRP2 to activate Wnt/β-catenin signaling pathway, indicating that METTL3 might be a promising predictor in NSCLC. 

摘要翻译： 

本研究旨在探讨m6A调控因子METTL3在非小细胞肺癌（NSCLC）中的作用。采用RT-qPCR检测m6A相关基因及SFRP2的mRNA表达，Western blot法检测ZEB1和MMP9蛋白表达水平。通过甲基化RNA免疫沉淀（MeRIP）实验测定总m6A水平，RIP实验检测SFRP2的m6A修饰水平。采用CCK-8和Transwell实验分析细胞行为，并通过异种移植实验进一步验证METTL3和SFRP2在NSCLC中的作用。结果显示：NSCLC组织中METTL3表达水平显著高于正常对照组；下调METTL3可抑制NSCLC细胞增殖、迁移和侵袭能力，而上调METTL3则产生相反效应。研究发现METTL3负向调控SFRP2表达。值得注意的是，在NSCLC细胞表型和异种移植小鼠模型中，敲低METTL3产生的抗肿瘤效应可通过抑制SFRP2被逆转。沉默METTL3可增强SFRP2 mRNA稳定性。最终研究发现，METTL3通过下调SFRP2激活Wnt/β-catenin信号通路。METTL3通过抑制SFRP2激活Wnt/β-catenin信号通路，在NSCLC发病机制中发挥癌基因功能，表明METTL3可能成为NSCLC潜在的预后预测指标。

原文链接：

METTL3 promotes the malignancy of non-small cell lung cancer by N6-methyladenosine modifying SFRP2