Rce1 Expression In Renal Cell Carcinoma And Its Regulatory Effect On 786-O Cell Apoptosis Through Endoplasmic Reticulum Stress

Objective: Ras and a-factor-converting enzyme 1(Rce1)is located in the endoplasmic reticulum(ER)and is thought to be responsible for endoproteolytic processing of the vast majority of CAAX proteins.Endoplasmic reticulum stress(ERS)plays an important role in renal cell carcinoma(RCC);however,the expression and role of Rce1 in RCC has not been extensively studied.We aimed to investigate the expression of Rce1 in RCC tissues and its molecular mechanism in ERS-induced apoptosis in RCC 786-O cells.Methods: We first used western blotting,quantitative reverse transcriptasepolymerase chain reaction,and immunohistochemistry to detect the Rce1 expression in renal carcinoma tissues and paracancerous tissues.Next,we detected the expression of Rce1 in human embryonic kidney cell line HEK293 and human renal carcinoma cell lines 786-O,ACHN,and A498.After we knocked-down Rce1 in 786-O cells,FCM and cck-8 were used to detected the change of apoptosis and proliferation.Finally,we used western blotting to detect the expressions of intracellular endoplasmic reticulum stress(ERS)PERK-e IF2?-ATF4 signaling factors and pro-apoptotic protein Bax,and down-regulate expression of Bcl-2.Results: It was found that Rce1 expression was upregulated in RCC tissues,and its positive expression level was strongly associated with clinicopathologic features.Higher expression of Rce1 was found in human renal carcinoma cell lines,especially in 786-O cells.Knockdown of Rce1 in 786-O cells increased apoptosis and inhibited proliferation(P < 0.05).Moreover,downregulation of Rce1 upregulated the expression of the pro-apoptotic protein Bax,but downregulated the expression of the anti-apoptotic protein Bcl-2.Further studies showed that down-regulation of Rce1 also affected the expression of ER stress factors.Conclusions: our results indicated that Rce1 plays a key role in RCC.Low expression of Rce1 might indirectly increase apoptosis and inhibit proliferation of renal carcinoma cells through ERS.