Abstract
BACKGROUND: Multiple myeloma (MM) is a major hematologic malignancy with limited therapeutic progress in radiotherapy. Although radiotherapy is widely used for palliation, its molecular effects in MM remain poorly defined. This study identifies RPL29 as a novel radiotherapy-responsive gene in MM and evaluates its prognostic and therapeutic relevance. METHODS: We employed a multidisciplinary approach, including murine models, radiotherapy schedules, RNA sequencing (RNA-seq), quantitative polymerase chain reaction (qPCR), and bioinformatics. Clinical samples from MM patients (age, sex, and ethnicity recorded) were included for validation. Statistical analysis aimed to identify differentially expressed genes and assess their prognostic significance. Differential gene expression analysis was conducted on irradiated and control groups. Venn diagram analysis and protein-protein interaction (PPI) network construction were used to identify key regulatory genes. RESULTS: RNA-seq analysis revealed 424 upregulated and 33 downregulated genes in the 2 Gy local tumor radiotherapy group compared to control. The tumor suppressor gene ADIPOQ emerged as a hub gene in the PPI network. Among the validated downregulated genes was UPK3A, while RPL29, not RPL19, was found to be consistently downregulated in the 2 Gy group. This finding was replicated in MM cell lines and patient samples, supporting its role in disease progression. Distinct radiotherapy doses and delivery methods induced specific biological processes and KEGG pathways, underscoring dose-dependent transcriptional effects. CONCLUSIONS: RPL29 downregulation following 2 Gy radiotherapy correlates with improved prognosis in MM, highlighting its potential as a clinically relevant prognostic biomarker. These findings provide new insights into MM biology and establish a foundation for targeted therapeutic strategies involving RPL29 and related pathways.