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

Abdul Jamil Khan; Islam Uddin Khan; Shad Man; Shihao Liu; Gaowa Ailun; Manzar Abbas; Feng Zhang

doi:10.1007/s13205-024-04196-z

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

3 Biotech. 2025 Feb;15(2):37. doi: 10.1007/s13205-024-04196-z. Epub 2025 Jan 9.

Authors

Abdul Jamil Khan¹, Islam Uddin Khan², Shad Man³, Shihao Liu⁴, Gaowa Ailun⁵, Manzar Abbas⁶, Feng Zhang^{7

8}

Affiliations

¹ Biomedical Nanocenter, School of Life Science, Inner Mongolia Agricultural University, Hohhot, 010018 China.
² Complete Genomics Biochemistry-1, Department US CG Biochem, MGI Tech Co., Ltd. Beishan Industrial Zone, Yantian District, Shenzhen, 518083 China.
³ Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, School of Life Sciences, Inner Mongolia University, Hohhot, 010020 China.
⁴ Department of Informatics and Computer Engineering, Simon Kuznets Kharkiv National University of Economics, Nau Kyaveave., 9-A, Kharkiv, 61166 Ukraine.
⁵ The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, 010050 China.
⁶ Inner Mongolia Saikexing Institute of Breeding and Reproductive Biotechnology in Domestic Animal, Hohhot, 011500 China.
⁷ Key Laboratory of Optical Technology and Instrument for Medicine, Ministry of Education, University of Shanghai for Science and Technology, Shanghai, 200093 China.
⁸ Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, 325001 China.

PMID: 39802327
PMCID: PMC11718041 (available on 2026-02-01)
DOI: 10.1007/s13205-024-04196-z

Abstract

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.

Keywords: Biomarker; Breast cancer; C-MYC; Chemo-resistance; Ferroptosis; MRPL24; Metastasis; Stemness.

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