Bi Qiufen, Nie Jun, Wu Qiang, Sun Liang, Zhu Shuang, Bai Jin, Liu Yong, Huang Fang, Chai Keli
Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, China.
Med Oncol. 2025 Feb 1;42(3):60. doi: 10.1007/s12032-025-02604-9.
Tumor metabolic reprogramming, particularly involving mitochondrial metabolism, is a hallmark of malignancy. The mitochondrial protein p32 (C1QBP) has emerged as a critical regulator in various cancers, frequently associated with poor patient prognosis. However, the role of p32 across different cancer types remains largely unexplored. Our bioinformatics analysis demonstrates that p32 is significantly overexpressed in several malignancies and is closely involved in multiple oncogenic pathways related to tumor progression and metabolic reprogramming. Moreover, p32 expression positively correlates with genomic heterogeneity and drug sensitivity. We identified a strong association between p32 and c-Myc in both normal and cancerous tissues. We confirmed that p32 is a direct transcriptional target of c-Myc, which upregulates p32 by binding to its promoter. Functional experiments established that p32 is crucial for MYC-driven tumorigenesis, with its knockdown or knockout inhibiting tumor proliferation and extending survival. Targeting p32 may inhibit MYC-driven tumorigenesis, highlighting its potential as a therapeutic target in MYC-driven cancers.
肿瘤代谢重编程，尤其是涉及线粒体代谢的重编程，是恶性肿瘤的一个标志。线粒体蛋白p32（C1QBP）已成为各种癌症中的关键调节因子，常与患者预后不良相关。然而，p32在不同癌症类型中的作用在很大程度上仍未得到探索。我们的生物信息学分析表明，p32在几种恶性肿瘤中显著过表达，并密切参与与肿瘤进展和代谢重编程相关的多种致癌途径。此外，p32表达与基因组异质性和药物敏感性呈正相关。我们在正常组织和癌组织中均发现p32与c-Myc之间存在强关联。我们证实p32是c-Myc的直接转录靶点，c-Myc通过结合其启动子上调p32。功能实验表明，p32对MYC驱动的肿瘤发生至关重要，敲低或敲除p32可抑制肿瘤增殖并延长生存期。靶向p32可能抑制MYC驱动的肿瘤发生，突出了其作为MYC驱动癌症治疗靶点的潜力。
