The tumor-repressing effect of CYP27A1 on renal cell carcinoma by 27-HC arising from cholesterol metabolism

CYP27A1对胆固醇代谢产生的27-HC对肾细胞癌的抑癌作用

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作者:Xingming Zhang, Xiaoxue Yin, Jindong Dai, Guangxi Sun, Haoran Zhang, Jiayu Liang, Jinge Zhao, Sha Zhu, Junru Chen, Xudong Zhu, Yuchao Ni, Zhipeng Wang, Zhenhua Liu, Ni Chen, Pengfei Shen, Hao Zeng

Abstract

As a key approach to mediate cholesterol metabolism, the role of the CYP27A1/27-HC axis in renal cell carcinoma (RCC) remains unclear. Analysis of CYP27A1 expression from public databases and metastatic cases in our center suggested that CYP27A1 was obviously downregulated in RCC tissues, and survival analysis further showed its correlation with favorable clinicopathological features and prognosis. In vitro, up and downregulation of CYP27A1 expression in RCC cell lines could definitely illustrate its anticipation involving apoptosis, proliferation, invasion, migration, and clonality. This could be achieved through upregulation of 27-HC concentration, which mediates the activation of signaling pathways of apoptosis and cell cycle arrest. Further, recovery of CYP27A1 expression could definitely inhibit the proliferation of RCC tumors in vivo. This is the first study to explore the role of the CYP27A1/27-HC axis in RCC. Attempts to maintain the normal function of the axis may be a potential strategy in the treatment of RCC, and the predictive value of CYP27A1 detection on the efficacy of targeted therapy in metastatic RCC is also worthy of attention.

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