MRPL24 drives breast cancer metastasis and stemness by targeting c-MYC, BRD4, and STAT3.

The study aims to investigate the clinicopathological significance of MRPL24 in human cancers, with a particular focus on breast cancer (BC). Comprehensive bioinformatics analyses were conducted using data from The Cancer Genome Atlas (TCGA) and various advanced database, including cBioPortal, UALCAN, TIMER, Prognoscan, TISIDB, KM Plotter, and The Human Protein Atlas, to provide a detailed evaluation of MRPL55's role in cancer. The findings were further validated through experimental studies. Pan-cancer analysis of TCGA/ICGC data revealed significant amplification of MRPL24 across multiple cancer types, with the highest amplification rate of 60% observed in metastatic breast cancer. MRPL24 was found to be overexpressed in primary breast tumors, metastatic, and various molecular subtypes of breast cancer. High MRPL24 expression was associated with poor prognosis and lower survival rates in breast cancer patients. RT-PCR and western blot confirmed MRPL24 depletion in breast cancer cells. Knockdown of MRPL24 was shown to suppress proliferation, and clonogenic potential in breast cancer cells and inhibit cell migration. Additionally, MRPL24 depletion sensitized breast cancer cells to PD0325901 and 5-FU treatment. Mechanistic studies revealed that MRPL24 knock-down downregulates mRNA levels of oncogenic genes, including c-MYC, BRD4, WNT3, and STAT3. Positive correlations were observed between MRPL24 and key genes involved in ferroptosis regulation, such as ERBB2, ERBB3, GRB2, PIK3CA, AKT1, MAPK3, and MAPK1. Finally, through virtual screening and molecular dynamics simulations, we have identified three FDA-approved drugs with strong binding affinities and interactions with MRPL24. These findings underscore MRPL24's oncogenic role in breast cancer and suggest potential therapeutic strategies targeting this protein.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04196-z.