Identification of WTAP target genes by high-throughput RNA-seq and m6A-seq. (A) The consensus motif was identified by HOMER with m6A-seq peaks in SU-DHL-8 cells with or without WTAP knockdown. (B) Graphs of m6A peak distribution showing the proportion of total m6A peaks in the indicated regions in control and WTAP-deficient cells. CDS, coding sequence; TSS, transcription start site. (C) Distribution of transcripts with a significant change in both m6A level and expression level in WTAP knockdown compared with control SU-DHL-8 cells. (D) Gene set enrichment analysis plots for WTAP-regulated genes, as determined by RNA-seq. (E) The m6A abundances in HK2 mRNA transcripts in WTAP knockdown and control SU-DHL-8 cells. (F) Relative mRNA levels of HK2 from qPCR analysis in WTAP knockdown compared with control DLBCL cells. (G) Gene-specific m6A qPCR validation of m6A level changes in HK2 in WTAP knockdown compared with control DLBCL cells. (H) Dual-luciferase reporter assays showed the effect of WTAP on HK2 reporters with either WT or MUT binding sites. (I) Schematic diagram of knocking out the m6A RNA methylation site on the 5′ UTR of HK2 using the CRISPR-Cas9 genome editing method. (J) Farage-knockout (Farage-KO) cells (si-NC or si-WTAP-transfected) were harvested at 24, 48, and 72 hours after transfection. Cell proliferation was assessed by CCK-8 assays. Error bars represent the mean ± SD of 3 independent experiments. **P < .01; ****P < .0001.