ECHS1 suppresses renal cell carcinoma development through inhibiting mTOR signaling activation

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.