EIF4A3 (Eukaryotic Translation Initiation Factor 4A3)

The bindings of circFGFR3 to EIF4A3 and EIF4A3 to JAK2, STAT3, or STAT5 were analyzed. In conclusion, RBM15 promotes PD-L1-mediated immune escape and accelerates OC progression by upregulating circFGFR3 expression through m6A modification and activating the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway.

SELENOF and eIF4a3 were also higher in tissues derived from African American women, who also exhibited higher frequency of a SELENOP polymorphism in the non-coding region of the gene These findings suggest that SELENOF, eIF4a3, and SELENOP may contribute to breast cancer progression and racial disparities in outcomes. Their differential expression and genetic variation highlight potential molecular mechanisms underlying these disparities and may inform future therapeutic or diagnostic strategies.

In vivo, circEIF2S2 depletion significantly inhibited tumor growth and liver metastasis in xenograft models. Collectively, these findings identify the EIF4A3-circEIF2S2-miR-646-UHMK1 axis as an important regulatory pathway involved in CRC progression and tumor-associated immunosuppression.

Therapeutic targeting of this axis with the EGFR inhibitor gefitinib restored oxaliplatin sensitivity in vitro and synergistically suppressed RBM8A-driven xenograft growth in vivo. Additionally, single-cell RNA-seq revealed RBM8A enrichment in malignant gastric epithelial cells, while tissue microarrays confirmed that dual RBM8A/EGFR overexpression predicts the poorest survival outcomes. Collectively, our findings define the RBM8A-eIF4A3-EGFR axis as a druggable determinant of chemoresistance and establish RBM8A as both a prognostic biomarker and therapeutic target in GC.

Surface residue mapping of SMG1 kinase revealed that it engages with SMG8, SMG9, and UPF1 in a sequential binding order, displaying the highest affinity for SMG8. Overall, these findings contribute to the mechanistic understanding of molecular properties for different RBPs from the NMD process, which can be the basis of developing new therapeutic strategies against genetic disease or cancer.

These findings identify circDNAJC16 downregulation as a negative prognostic indicator in LUAD and reveal its dual tumor-suppressive roles: cytoplasmic sequestration of miR-93-5p activating CDKN1A-mediated cell cycle arrest, coupled with eIF4A3-governed nuclear retention controlling functional subcellular localization. Significantly, this work is the first to demonstrate eIF4A3-mediated circRNA compartmentalization, establishing circDNAJC16 as a novel prognostic biomarker and therapeutic target for LUAD.

Finally, inhibiting circCNOT6L overexpression in combination with the ferroptosis activator (erastin) significantly suppressed the viability of PCa-derived organoids. In conclusion, in the present study, we found that circCNOT6L induced by EIF4A3 through the SRSF2-SLC7A11 axis effectively inhibits ferroptosis, which in turn promotes malignant progression of PCa.

These findings reveal a novel mechanism by which circPVT1 contributes to RCC, highlighting the potential of the cP104aa peptide as a therapeutic target. Axitinib may serve as an effective therapeutic agent for patients with advanced RCC exhibiting high cP104aa expression.

In conclusion, this study demonstrates that circCRIM1 may play a crucial role in modulating the translation of HIF-1α mRNA through its interaction with PTBP3, ultimately influencing the expression of VEGFA, a key factor in angiogenesis and tumor growth. The results emphasize the importance of circCRIM1 in cancer biology and their potential as therapeutic targets for GBM.

These findings establish circZFR as a pivotal driver of cervical cancer progression and highlight its inhibition as a promising therapeutic strategy.

Moreover, EIF4A3 has binding sites in the upstream region of the GNAI2 pre-mRNA, and we confirmed that circGNAI2 was downregulated by EIF4A3 in TNBC cells. Overall, our study indicates that EIF4A3-regulated circGNAI2 suppresses TNBC progression possibly by regulating the miR-454-3p/VGLL4/STAT3 pathway, providing pivotal potential therapeutic targets for the treatment of TNBC.