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.
Conclusions
METTL3 promotes translation of NEDD1 via YTHDF1-depedndent m6A modification, thereby activating the Hedgehog signaling pathway to promote immune escape of DLBCL cells.
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.