Vimentin Regulates Alternative Polyadenylation and mTOR Signaling via ARVCF to Promote B Cell Lymphoma Progression

Background: Vimentin (VIM), a cytoskeletal protein implicated in tumor progression, has been associated with poor prognosis in B cell lymphomas. Alternative polyadenylation (APA), a posttranscriptional mechanism that modulates mRNA isoforms via 3 ′ UTR length changes, is frequently dysregulated in cancer. The interaction between VIM and APA in B cell lymphoma remains poorly understood. Methods: We performed RNA‐seq, APA analysis (DaPars), and proteomic profiling in wild‐type and VIM‐knockout (VIM‐KO) B cell lymphoma cells (A20 and M12). Functional assays including CCK‐8, EdU, Western blot, and ARVCF overexpression were used to explore the regulatory axis involving APA and mTOR signaling. Results: VIM deletion in B cell lymphoma cells triggered widespread transcriptome remodeling, inducing 4089 APA shortening events that preferentially targeted prosurvival pathways, for example, mTORC1, G2‐M checkpoint. Strikingly, RRAGA—a critical mTOR activator—underwent 3 ′ UTR shortening, concomitant with ARVCF downregulation in proteomic profiles. Functional rescue experiments demonstrated ARVCF’s dual role in maintaining RRAGA 3 ′ UTR length and suppressing mTOR‐EIF4G1 signaling, ultimately inhibiting lymphoma proliferation. Conclusion: This study reveals a novel VIM–ARVCF–RRAGA–mTOR axis in B cell lymphoma, linking cytoskeletal disruption to APA‐mediated oncogenic signaling. VIM loss drives APA shortening and mTOR activation via ARVCF downregulation, promoting lymphoma progression. These findings offer mechanistic insight and potential targets for therapeutic intervention.