SELENOF and its translational inhibitor EIF4A3 are differentially expressed in colon cancer.

Selenoproteins are critical regulators of redox homeostasis, protein folding, and metabolism, and their dysregulation has been implicated in cancer biology. Among them, selenoprotein F (SELENOF) has been reported to be tumor suppressive, whereas the RNA-binding protein EIF4A3, a component of the exon junction complex, has been implicated in post-transcriptional repression of selenoproteins. The regulatory and clinical significance of this interaction in colorectal adenocarcinoma (COAD) remains unclear. We performed an integrative analysis of transcriptomic data from The Cancer Genome Atlas (TCGA), proteomic data from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and patient tissue microarrays. Western blotting, qRT-PCR, and immunofluorescence staining were used to examine SELENOF, GPX1, and EIF4A3 expression in colon cancer cell lines and tumor tissues. Correlation, regression, and survival analyses were conducted, and pathway enrichment was assessed using gene set enrichment analysis (GSEA) of RNA and proteome correlation profiles. Motif discovery and translational efficiency analyses were performed to identify 3'-UTR features associated with EIF4A3 repressive activity. SELENOF and EIF4A3 showed inverse, stage-dependent protein expression patterns in COAD in the CPTAC cohort. Survival analyses demonstrated that SELENOF alone was not prognostic but acquired significance in EIF4A3-high tumors, where low SELENOF was associated with poor outcomes. Motif analyses identified enriched 3'UTR elements in SELENOF, suggesting that EIF4A3 represses translation through non-SECIS motifs positioned near canonical SECIS elements. Our findings explore a novel EIF4A3-SELENOF regulatory axis in colorectal cancer. SELENOF acquires conditional prognostic significance only in the context of elevated EIF4A3, highlighting the importance of molecular interaction specificity in biomarker discovery.