RNF25 serves as a novel diagnostic and prognostic biomarker in multiple myeloma: a multi-cohort integrative analysis

TL;DR

This study identifies RNF25 as a new biomarker for diagnosing and predicting outcomes in multiple myeloma, linking it to poor survival and cancer cell behavior.

Contribution

The study introduces RNF25 as a novel diagnostic and prognostic biomarker in multiple myeloma through multi-cohort analysis.

Findings

RNF25 is consistently overexpressed in multiple myeloma datasets and is linked to worse overall survival.

RNF25 knockdown reduces cancer cell viability, proliferation, and migration while promoting apoptosis.

High RNF25 expression correlates with reduced immune scores and increased plasma cell infiltration.

Abstract

Ubiquitination-related genes (UbRGs) play critical roles in tumor biology. However, their functions in multiple myeloma (MM) remain insufficiently explored.

Transcriptomic data from public databases were integrated to identify UbRGs in MM through WGCNA, differential expression, and protein–protein interaction (PPI) analyses. Functional roles were examined by GO, KEGG, and GSEA, while immune infiltration and drug sensitivity were evaluated using CIBERSORT, ESTIMATE, and OncoPredict. UbRG expression was validated in clinical samples and cell lines by qRT-PCR and western blot, and functional effects of UbRG knockdown in MM cells were examined using CCK-8, Transwell, EdU, and TUNEL assays.

Ring Finger Protein 25 (RNF25) is a ubiquitination-related gene closely associated with MM, exhibiting consistent overexpression across multiple independent datasets. Elevated RNF25 expression is significantly correlated with poorer overall survival and serves as an independent adverse prognostic factor. Functional enrichment analysis revealed that RNF25 may regulate key pathways such as ATP-dependent chromatin remodeling, cell cycle progression, and ubiquitin-mediated proteolysis. Immune analysis further indicated that high RNF25 expression is associated with reduced immune and stromal scores, increased plasma cell infiltration, and elevated T cell co-inhibition activity. RNF25 was highly expressed in tumor tissues from clinical samples, and its knockdown significantly reduced the viability, proliferation, and migration of U266 cells, while promoting apoptosis.

RNF25 may serve as a potential prognostic biomarker for MM and holds promise as a candidate therapeutic target.

The online version contains supplementary material available at 10.1186/s41065-025-00631-0.

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