MRPL55 promotes BC progression as a prognostic biomarker by modulating lipogenesis and cyclin-dependent kinase pathways, from multi-omics to drug repurposing.

BACKGROUND

The mitochondrial ribosomal protein (MRP) family plays a pivotal role in tumorigenesis and has been linked to the advancement of various malignancies. Among them, MRPL55 has emerged as a protein of growing interest; however, its precise biological function and clinical significance, particularly in breast cancer, largely remain unknown.

METHODS

In this study, a comprehensive bioinformatics analyses were performed using multiple databases, including TCGA, cBioPortal, UALCAN, TISIDB, KM Plotter, TIMER, DriverDBv4, PrognoScan, HPA, GEPIA, GeneMANIA, bc-GenExMiner v5.0, and OncoDB etc. Experimental validation was carried out to confirm the expression and functional impact of MRPL55 in BC cell lines. In addition, virtual screening and molecular dynamics simulations were employed to identify candidate drugs targeting MRPL55.

RESULTS

MRPL55 is significantly overexpressed in breast cancer at both the mRNA and protein levels and Its expression correlates with advanced pathological stage, higher histological grade, lymph node involvement, and metastasis, and is associated with poor prognosis and reduced overall survival. Immune profiling revealed a strong inverse relationship between MRPL55 expression and infiltration of immune cells, including CD4⁺/CD8⁺ T cells, B cells, macrophages, neutrophils, and dendritic cells. Somatic copy number alterations in MRPL55 were linked to decreased immune infiltration and worse outcomes. Promoter hypomethylation and gene amplification may contribute to its overexpression. MRPL55 expression positively correlated with lipogenesis-related genes (e.g., SREBF1, FASN) and CDKs (e.g., CDK4, CDK10), and was associated with activation of key oncogenic pathways such as NRF2, WNT, and mTOR. Functional knockdown of MRPL55 in MCF-7 and MDA-MB-231 cells suppressed proliferation, migration, and survival, and downregulated lipogenic and CDK genes. Virtual screening and molecular dynamics identified three FDA-approved drugs with high binding affinity to MRPL55, suggesting potential for therapeutic repurposing. In conclusion, our findings establish MRPL55 as a potential oncogenic driver in luminal and metastatic breast cancer. Its involvement in lipogenesis, cell cycle regulation, and immune suppression highlights its prognostic value and therapeutic potential.