Jian Dan, Hu Nana, He Rong, He Le, Xiao He, Peng Xingqiao, Peng Yang, Yang Yuxin, Dai Xiaoyan, Wang Dong, Feng Yan, Dai Nan, Chen Qian
Cancer Center of Daping Hospital Army Medical University, No. 10 Changjiang Zhi Rd., Yuzhong Dist, Chongqing, 400042, China.
Yu-Yue Pathology Scientific Research Center, Chongqing, 401329, China.
Discov Oncol. 2025 Jul 2;16(1):1253. doi: 10.1007/s12672-025-03053-6.
Mitochondrial pyruvate carrier (MPC), composed of MPC1 and MPC2, plays a pivotal role in regulating cancer metabolism. While previous studies have implicated MPC1 in tumor progression, the specific function of MPC2 in renal cell carcinoma (RCC) remains largely unclear. In this study, we found that reduced MPC2 expression was significantly associated with advanced TNM stage and poor patient prognosis. Functional assays demonstrated that MPC2 suppresses RCC cell proliferation both in vitro and in vivo. Additionally, concurrent low expression of MPC2 and MPC1 was correlated with significantly shorter overall survival, suggesting their combined prognostic value. Gene set enrichment analysis indicated that both MPC1 and MPC2 are negatively associated with the Bmi1 signaling pathway. Mechanistically, inhibition of the MPC complex-either genetically or pharmacologically-led to increased Bmi1 protein levels by reducing its ubiquitin-mediated degradation. These findings identify the MPC complex as a potential tumor suppressor and prognostic biomarker set in RCC, functioning in part through modulation of Bmi1 stability.
线粒体丙酮酸载体（MPC）由MPC1和MPC2组成，在调节癌症代谢中起关键作用。虽然先前的研究表明MPC1与肿瘤进展有关，但MPC2在肾细胞癌（RCC）中的具体功能仍不清楚。在本研究中，我们发现MPC2表达降低与晚期TNM分期及患者预后不良显著相关。功能分析表明，MPC2在体外和体内均能抑制RCC细胞增殖。此外，MPC2和MPC1同时低表达与总生存期显著缩短相关，提示它们具有联合预后价值。基因集富集分析表明，MPC1和MPC2均与Bmi1信号通路呈负相关。机制上，通过基因或药理学方法抑制MPC复合物会降低Bmi1蛋白的泛素介导降解，从而导致Bmi1蛋白水平升高。这些发现表明MPC复合物是RCC中一种潜在的肿瘤抑制因子和预后生物标志物，部分通过调节Bmi1稳定性发挥作用。
