EIF3m is the latest identified subunit of the eukaryotic translation initiation factor 3 (eIF3), however, its function in malignant tumor is rarely reported. In the current work, we observed that EIF3m was aberrant over-expressed in lung adenocarcinoma (LADC) tissues and cell lines, and the increased EIF3m level was closely related to the poor clinical outcomes of the LADC patients. The gain- and loss-of-function assays demonstrated the proto-oncogenetic potential of EIF3m in vitro and in vivo . EIF3m induced-malignant phenotype was partly mediated by the up-regulation of CAPRIN1. The biochemical analysis showed that EIF3m could bind to the 5’UTR of CAPRIN1 and positively modulate its expression at the post-transcription level. Furthermore, we identified the interaction between EIF3m and the deubiquitinase UCHL5, which stabilized and promoted the accumulation of EIF3m in LADC cells. In summary, our findings extended the knowledge about the EIF3m function and highlight the roles of the UCHL5/EIF3m/CAPRIN1 axis during the progression of LADC.
RNAs and RNA-binding proteins (RBPs) play crucial roles in stress granule (SG) dynamics, yet the specific interactions between SG-associated circular RNAs (circRNAs) and RBPs in esophageal squamous cell carcinoma (ESCC) remain unclear. In this study, we identified m6A-modified circG3BP1 as a potential prognostic biomarker in ESCC. Under cisplatin-induced stress, IGF2BPs facilitate the m6A-dependent translocation of circG3BP1 to SGs, where it functions as a scaffold to enhance TIAR-CAPRIN1 interactions, thereby promoting SG nucleation. SG formation suppresses the translation of senescence-associated mRNAs, such as p21 , delaying chemotherapy-induced cellular senescence and contributing to cisplatin resistance in ESCC cells. Clinically, elevated circG3BP1 expression is associated with cisplatin resistance in patients with ESCC. These findings reveal a previously uncharacterized m6A-dependent mechanism by which circG3BP1 promotes SG-mediated chemoresistance, providing a promising potential biomarker and therapeutic target for ESCC treatment.
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