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

Lili Feng, Qinying Yan, Hui Pan, Wodong Shi

Immunity, inflammation and disease 2023 Feb

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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. 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. 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. METTL3 promotes translation of NEDD1 via YTHDF1-depedndent m6A modification, thereby activating the Hedgehog signaling pathway to promote immune escape of DLBCL cells. © 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.

Citation

Lili Feng, Qinying Yan, Hui Pan, Wodong Shi. METTL3 enhances the effect of YTHDF1 on NEDD1 mRNA stability by m6A modification in diffuse large B-cell lymphoma cells. Immunity, inflammation and disease. 2023 Feb;11(2):e789