Khan Abdul Jamil, Khan Islam Uddin, Man Shad, Liu Shihao, Ailun Gaowa, Abbas Manzar, Zhang Feng
Biomedical Nanocenter, School of Life Science, Inner Mongolia Agricultural University, Hohhot, 010018 China.
Complete Genomics Biochemistry-1, Department US CG Biochem, MGI Tech Co., Ltd. Beishan Industrial Zone, Yantian District, Shenzhen, 518083 China.
3 Biotech. 2025 Feb;15(2):37. doi: 10.1007/s13205-024-04196-z. Epub 2025 Jan 9.
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.
The online version contains supplementary material available at 10.1007/s13205-024-04196-z.
本研究旨在探讨MRPL24在人类癌症中的临床病理意义，尤其关注乳腺癌（BC）。使用来自癌症基因组图谱（TCGA）和各种先进数据库（包括cBioPortal、UALCAN、TIMER、Prognoscan、TISIDB、KM Plotter和人类蛋白质图谱）的数据进行了全面的生物信息学分析，以详细评估MRPL55在癌症中的作用。研究结果通过实验研究进一步验证。对TCGA/ICGC数据的泛癌分析显示，MRPL24在多种癌症类型中显著扩增，在转移性乳腺癌中观察到的最高扩增率为60%。发现MRPL24在原发性乳腺肿瘤、转移性乳腺癌以及乳腺癌的各种分子亚型中均过表达。MRPL24高表达与乳腺癌患者的不良预后和较低生存率相关。逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹法（western blot）证实了乳腺癌细胞中MRPL24的缺失。MRPL24的敲低显示可抑制乳腺癌细胞的增殖、克隆形成潜力并抑制细胞迁移。此外，MRPL24的缺失使乳腺癌细胞对PD0325901和5-氟尿嘧啶（5-FU）治疗敏感。机制研究表明，MRPL24的敲低下调了致癌基因的mRNA水平，包括c-MYC、BRD4、WNT3和STAT3。观察到MRPL24与铁死亡调节相关的关键基因（如ERBB2、ERBB3、GRB2、PIK3CA、AKT1、MAPK3和MAPK1）之间存在正相关。最后，通过虚拟筛选和分子动力学模拟，我们确定了三种美国食品药品监督管理局（FDA）批准的与MRPL24具有强结合亲和力和相互作用的药物。这些发现强调了MRPL24在乳腺癌中的致癌作用，并提出了针对该蛋白的潜在治疗策略。
在线版本包含可在10.1007/s13205-024-04196-z获取的补充材料。
