Fig 2: Characteristics of the m6A-modified lncRNA microarray in LUAD tumor tissues and adjacent normal tissues. A The source distribution of m6A-modified lncRNA transcripts. B The length distribution of m6A-modified lncRNA transcripts (≤ 3000 bp). C The chromosomal localization of m6A-modified lncRNA transcripts. D Volcano plot showed that in 2846 m6A-modified lncRNA transcripts, 143 were differentially modified (|log2FC|> 0.585, P < 0.05, unpaired t test), and 123 were hypermethylated and 20 were hypomethylated. E The methylation level heatmap of 143 differentially modified lncRNA transcripts. F Volcano plot showed that in 143 differentially modified lncRNA transcripts, 32 were upregulated and 48 were downregulated (|log2FC|> 1, P < 0.05, unpaired t test). G The expression level heatmap of 143 differentially modified lncRNA transcripts

Fig 3: The screening of prognostic m6A-regulated lncRNAs. A The screening criteria of 215 m6A-regulated lncRNAs and its expression correlation with m6A regulators. B Forest plot of univariate Cox regression analysis of m6A-regulated lncRNAs (P < 0.01). The hazard ratio (HR) value, its 95% confidence interval (CI), as well as the associated P value, were shown. HR > 1 indicated that the lncRNA was a risk factor and its high expression was unfavorable for prognosis, while the high expression of the protective lncRNA of HR < 1 was favorable for prognosis. C The expression correlation between 13 prognostic m6A-regulated lncRNAs and m6A regulators

Fig 4: m6A methylation decreases upon METTL3 inhibition or degradation.(A) EpiPlex analysis of global number of m6A (blue) and inosine (red) peaks upon STM2457 inhibitor (STM) or dTAG degrader treatment, compared to the DMSO control (DMSO). The error bars indicate the standard deviation of three technical replicates per condition. (B) m6A and inosine enrichment data of the DNAJ14 gene transcript upon STM2457 inhibitor or dTAG degrader treatment. The gene tracks illustrate a decrease in m6A enrichment in the treated conditions, while the inosine levels remain largely unchanged.

Fig 5: LINC00839 promotes c-Src-mediated β-catenin phosphorylation.A The enrichment of c-Src in pull-down products of LINC00839 was measured by western blot. B RNA immunoprecipitation with an anti-c-Src antibody was used to assess whether c-Src binding to LINC00839 in GSCs. C GSCs were transfected with or without RNase If. Immunoprecipitation with anti-β-catenin and anti-c-Src antibodies were performed. D GSCs were transfected with or without RNase If. IF assays were performed to analyze the co-localization of β-catenin (Red) and c-Src (Green). E GSCs were transfected with control or LINC00839 ASO. Immunoprecipitation with an anti-β-catenin antibody was performed. F Control or METTL3 deleted GSCs were co-transfected with LINC00839. Immunoprecipitation with an anti-β-catenin antibody was performed. G Control or YTHDF2 deleted GSCs were co-transfected with LINC00839. Immunoprecipitation with an anti-β-catenin antibody was performed. H. GSCs were transfected with FL or TL LINC00839. Immunoprecipitation with an anti-β-catenin antibody was performed. I In vitro β-catenin phosphorylation assay using recombinant β-catenin, c-Src proteins, and in vitro-transcribed RNA transcripts as indicated in NETN buffer with the presence of 500 µM ATP. Immunoblots were used to detect β-catenin phosphorylation level. J Luciferase activity (TOP/FOP) in control or LINC00839 overexpressing MES28 co-transfected with WT or Y654E mutation β-catenin. **p < 0.001. K Control or LINC00839 overexpressing GSCs were co-transfected with WT or Y654E mutation β-catenin. Representative images of spheres were photographed. Scale bars, 1 mm. L, M Control or LINC00839 overexpressing GSCs were co-transfected with WT or Y654E mutation β-catenin. The apoptotic rates were measured by flow cytometry. **p < 0.001.