Translational hub ribosomal protein S5 promotes glioblastoma progression by affecting translation patterns

). Functional experiments demonstrated that RPS5 silencing inhibited glioma malignant phenotypes both in vitro and in vivo. Mechanistically, RPS5 regulated translational processes in glioma cells, including start/stop codon recognition and cap-independent translation. Ribosome profiling (n = 3) coupled with RNA sequencing revealed that RPS5 enhanced the translational efficiency of SLC4A7 and MAK16, driving GBM progression. Furthermore, bicistronic reporter assays with rigorous controls (promoter-less vector, splicing analysis, and Rluc knockdown) demonstrated that the SLC4A7 5'UTR possesses cap-independent translation activity enhanced by RPS5, whereas RPS5 regulates MAK16 translation without relying on this cap-independent element. Our data reveal a pro-oncogenic role of RPS5 in glioma progression and highlight its critical function in regulating translation. These findings provide new evidence supporting the central role of ribosome protein-induced translational dysregulation in cancer and offer innovative perspectives for developing molecular therapies targeting GBM.