Alpha gene upregulates TFEB expression in renal cell carcinoma with t(6;11) translocation, which promotes cell canceration

: Renal cell carcinoma (RCC) with t(6;11) translocation has been characterized by the fusion of the Alpha gene with the TFEB gene. However, the underlying molecular mechanisms remain greatly uncharacterized and effective targeted therapy has yet to be identified. In this study, we examined the role of the Alpha gene in this tumor entity and the function of the fusion gene Alpha-TFEB product in vitro and in vivo. Our results revealed that the luciferase activity of Alpha1, Alpha2, Alpha3, Alpha4 and Alpha5 significantly increased compared with that of the pGL3-Basic group (P<0.01). The luciferase activity also increased significantly in the Alpha1, Alpha2 and Alpha5 groups compared with that of the normal TFEB gene group (P<0.01). In addition, the luciferase activity of Alpha5 was the strongest located in the 643-693 base sequence. The stable transfection of Alpha-TFEB into HK-2 and CaKi-2 cells promoted the expression of Alpha-TFEB mRNA and TFEB protein. Furthermore, the overexpression of TFEB increased cell proliferation and enhanced the cell invasive ability, and decreased cell apoptosis in the Alpha-TFEB stably transfected cells in vitro. In vivo experiments revealed that the overexpression of TFEB promoted tumorigenicity in nude mice, which was consistent with our in vitro results. On the whole, these data indicate that the overexpression of TFEB confers a potent oncogenic signal and may thus be a novel therapeutic target in RCC with t(6;11) translocation.