ECHS1 suppresses renal cell carcinoma development through inhibiting mTOR signaling activation
ECHS1 suppresses renal cell carcinoma development through inhibiting mTOR signaling activation
复制标题
ECHS1 通过抑制 mTOR 信号激活来抑制肾细胞癌的发展
DOI：
10.1016/j.biopha.2019.109750
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发表时间：
2020-03-01
影响因子：
7.5
通讯作者：
Zheng, Junfang
中科院分区：
文献类型：
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作者：
Wang, Lei;Qi, Yijun;Zheng, Junfang
尽管肾细胞癌（RCC）患者的管理近年来发生了巨大的变化，但它仍然面临着不断变化的挑战。阐明RCC的机制将有助于治疗方法的发展，以及早期诊断的生物标志物。本研究对不同分期患者的ccRCC组织进行了基于itraq的蛋白质组学分析。不同时期共发现130个共同差异表达蛋白（DEPs），脂质代谢途径在各时期均明显失调。这130个常见的dep富集在四个高度连接的子网络中，包括代谢途径、TCA循环、氧化磷酸化和脂肪酸代谢。进一步研究了脂肪酸代谢的关键酶ECHS1。ECHS1表达在ccRCC组织中显著下调，且ECHS1水平能很好地将ccRCC组织与相邻I期正常组织区分开来，且受者工作特征曲线下面积（AUC）大于0.7。ECHS1过表达通过抑制mTOR通路激活抑制RCC细胞增殖和迁移。ECHS1可能成为ccRCC治疗干预的新靶点和ccRCC的诊断性生物标志物。
Although the management of patients with renal cell carcinoma (RCC) has changed drastically in recent years, it is still faced with the evolving challenge. Elucidation of the mechanisms underlying RCC will help the development of therapies, as well as biomarkers for early diagnosis. In this study, ccRCC tissues from patients in different stages were subject to iTRAQ-based proteomics analysis. 130 common differentially expressed proteins (DEPs) in different stages were found and lipid metabolism pathway was obviously dysregulated in all stages. These 130 common DEPs were enriched in four highly connected subnetworks including metabolic pathway, the TCA cycle, oxidative phosphorylation and fatty acid metabolism. ECHS1, a key enzyme in fatty acid metabolism, was further investigated. ECHS1 expression was significantly downregulated in ccRCC tissues and ECHS1 level discriminated ccRCC tissues in general and in stage I from adjacent normal tissues well and with the area under the receiver operating characteristic curve (AUC) of more than 0.7. ECHS1 overexpression suppressed RCC cell proliferation and migration through inhibiting mTOR pathway activation. ECHS1 may be a novel target for ccRCC therapeutic interventions and diagnostic biomarker for ccRCC.