METTL3 enhances the effect of YTHDF1 on NEDD1 mRNA stability by m6A modification in diffuse large B‐cell lymphoma cells

AIM: Diffuse large B‐cell lymphoma (DLBCL) remains the most frequent subpopulation of lymphoma, and N6‐methyladenosine (m6A) was implicated in the DLBCL progression. Herein, we sought to decipher the m6A‐asociated mechanism of NEDD1 in DLBCL development. METHODS: The NEDD1 expression profile in DLBCL was assessed by quantitative real‐time polymerase chain reaction (RT‐qPCR) and Western blot. NEDD1 was artificially downregulated or upregulated in DLBCL cells, followed by EdU, Transwell assays and flow cytometry. The Hedgehog pathway activity was assayed by a dual‐luciferase assay. The m6A methylation of NEDD1 in DLBCL was assessed by meRIP‐qPCR, and the regulatory mechanism of METTL3 on NEDD1 was validated. The LDH assay was conducted to examine the impact of CD8(+) T cells on DLBCL cells. The DLBCL cells were administrated into mice to evaluate the tumorigenic activity and ki‐67 activity in tumor tissues. RESULTS: NEDD1 was overexpressed in DLBCL. Depletion of NEDD1 inhibited the aggressiveness of SU‐DHL‐8 and OCI‐LY1 cells, whereas overexpression of NEDD1 expedited the aggressiveness of SU‐DHL‐8 and OCI‐LY1 cells. METTL3 promoted NEDD1 translation in an m6A‐dependent manner via YTHDF1. Depletion of METTL3 inhibited SU‐DHL‐8 and OCI‐LY1 cell activity through regulation of NEDD1. NEDD1 reversed the repressive effect of METTL3 loss on the aggressiveness of SU‐DHL‐8 and OCI‐LY1 cells. NEDD1 activated the Hedgehog signaling to promote immune escape of DLBCL. CONCLUSIONS: METTL3 promotes translation of NEDD1 via YTHDF1‐depedndent m6A modification, thereby activating the Hedgehog signaling pathway to promote immune escape of DLBCL cells.