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

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/beta-catenin signaling pathway in NSCLC. METTL3 acted as an oncogene in the pathogenesis of NSCLC via suppressing SFRP2 to activate Wnt/beta-catenin signaling pathway, indicating that METTL3 might be a promising predictor in NSCLC.

Automated summary

This study aimed to investigate the roles of METTL3, a regulator of m6A, in NSCLC. They found that METTL3 was overexpressed in NSCLC and its downregulation restrained the proliferation, migration and invasion of NSCLC cells. They also discovered that METTL3 negatively regulated SFRP2 and its silencing enhanced the stability of SFRP2. Furthermore, downregulation of SFRP2 induced by METTL3 activated the Wnt/beta-catenin signaling pathway in NSCLC. Thus, METTL3 might be a promising predictor and therapeutic target for NSCLC.