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

Abstract

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.