VIRMA-Mediated the m6A Methylation of SCD Facilitates Wilms' Tumor Progression via AMPK Pathway

Wilms' tumor (WT) is the most prevalent renal cancer in children. Numerous studies have shown that vir-like n6-methyladenosine (m6A) methyltransferase-associated protein (VIRMA), a necessary component and the largest methyltransferase, contributes to the advancement of multiple cancers. However, its function has not been characterized in WT. Hence, we examined the potential role of VIRMA in WT by analyzing its effect on the m6A modification of stearoyl-CoA desaturase (SCD). We utilized bioinformatics to narrow 12 differentially expressed (DE) genes in WT to a single gene. The expressions of SCD and VIRMA were analyzed via quantitative real-time PCR and western blotting. The influence of SCD on the malignancy attributes of WT cells and adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling was assessed through Cell counting Kit-8, Ethynyl-2'-deoxyuridine, transwell, and western blotting assays. The specific interactions between SCD and VIRMA were confirmed through methylated RNA immunoprecipitation, western blotting, and RNA stability assays, followed by rescue experiments to show underlying mechanisms. The SCD expression was found to be elevated in WT samples. Furthermore, its silencing mitigated the malignant characteristics of WT cells while increasing the protein levels of key AMPK signaling molecules. Moreover, VIRMA was also upregulated in WT samples and demonstrated a positive association with SCD expression. The relative enrichment of SCD m6A, its protein, and its mRNA stability were enhanced in VIRMA-overexpressed WT cells. Mechanically, VIRMA overexpression accelerated the malignant phenotypes of WT cells by interacting with SCD. Overall, the results demonstrate that VIRMA-mediated m6A methylation of SCD promotes WT progression by modulating the AMPK pathway.