Feng Shoujie, Zhang Li, Sun Teng, Xu Lei, Quan Xiaoyu, Zhao Guoqing, Zhang Hao
Thoracic Surgery Laboratory, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of Thoracic Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
J Cell Mol Med. 2025 Jun;29(11):e70634. doi: 10.1111/jcmm.70634.
Non-small cell lung cancer (NSCLC) is a highly lethal malignant tumour characterised by its resistance to treatment, often due to metabolic reprogramming. Despite this, the underlying mechanisms by which aberrant cholesterol metabolism influences the development and progression of NSCLC remain unclear. In our study, we observed that OVOL1 is significantly upregulated in NSCLC and is correlated with a poor prognosis. Furthermore, our functional assays revealed that OVOL1 enhances the proliferation and metastasis of NSCLC cells both in vitro and in vivo. Mechanistically, OVOL1 was found to modulate cholesterol reprogramming and increase the expression of APOE, thereby intensifying cholesterol metabolism and facilitating cell migration and invasion. In conclusion, our findings suggest that OVOL1 acts as an oncogene in NSCLC, promoting tumour growth and metastasis through the enhancement of cholesterol metabolism. This underscores the potential of OVOL1 as a therapeutic target for the treatment of NSCLC.
非小细胞肺癌(NSCLC)是一种具有高度致死性的恶性肿瘤,其特征在于对治疗具有抗性,这通常归因于代谢重编程。尽管如此,异常胆固醇代谢影响NSCLC发生发展的潜在机制仍不清楚。在我们的研究中,我们观察到OVOL1在NSCLC中显著上调,并且与不良预后相关。此外,我们的功能分析表明,OVOL1在体外和体内均增强NSCLC细胞的增殖和转移。从机制上讲,发现OVOL1可调节胆固醇重编程并增加APOE的表达,从而加强胆固醇代谢并促进细胞迁移和侵袭。总之,我们的研究结果表明,OVOL1在NSCLC中作为癌基因发挥作用,通过增强胆固醇代谢促进肿瘤生长和转移。这突出了OVOL1作为NSCLC治疗靶点的潜力。