VIRMA promotes NSCLC progression by modifying ADAR m6A and increasing the activity of the TGF-β signaling pathway

Abstract

Abstract The N6-methyladenosine (m6A) modification is prevalently found in mRNAs and lncRNAs in various eukaryotic organisms, playing a crucial role in biological processes. Despite this, its contribution to non-small cell lung cancer (NSCLC) development and specific mechanisms remain unclear. We use bioinformatics analysis, real-time PCR, Western blotting and immunohistochemistry to analyze the expression of VIRMA and ADAR. Colony formation assays, transwell migration and invasion assay, cell apoptosis assay and Cell Counting Kit-8 assay was conducted to detect changes in cellular phenotype. Animal experiments were used to analyze the effect of VIRMA on the tumorigenic ability of A549. The activity of the TGF-β signaling pathway was evaluated by Western blotting. VIRMA is overexpressed in NSCLC and is associated with negative patient outcomes. Reducing VIRMA levels suppressed the growth, movement, and invasion of NSCLC cells while also increasing apoptosis in vitro. Additionally, VIRMA contributes to in tumor immunosuppression and NSCLC advancement by modifying its downstream target gene, ADAR, through methylation and enhanced activation of the TGF-β signaling pathway. Our study discovered a novel regulatory pathway involving VIRMA/ADAR/TGF-β in NSCLC. This provides new insights and a theoretical basis for developing novel immunotherapeutic targets.

Keywords

• VIRMA
• ADAR
• TGF-β signaling pathway
• m6A RNA methylation
• Non-Small cell lung cancer