TFEB promotes the progression of t(6; 11) translocation renal cell carcinoma by upregulating LINC00612 expression.

T(6;11) translocation renal cell carcinoma (RCC) is a distinct renal tumor distinguished by the generation of Alpha-TFEB fusion gene. TFEB is highly expressed in this subtype and may drive its progression. However, its underlying mechanism remains incompletely elucidated. The current study is intended to explore whether TFEB promotes the progression of t(6;11) translocation RCC by regulating long intergenic non-protein coding RNA (LINC)00612 expression. HK-2-TFEB and Caki-2-TFEB were stably transfected cell lines with Alpha-TFEB fusion gene, which were successfully established in our research group's previous work. Western blotting was carried out to assess TFEB protein expression, and qRT-PCR was employed to measure LINC00612, microRNA (miR)-31-5p and CTNNB1 expression levels. Bioinformatics analysis, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays were employed to validate the interactions between TFEB and LINC00612, LINC00612 and miR-31-5p, as well as miR-31-5p and CTNNB1. Wound healing, CCK-8 and invasion assays were used to verify the effects exerted by LINC00612 downregulation and upregulation, as well as CTNNB1 downregulation on the biological functionalities of cells. Experiments carried out in vivo were designed to assess the effects of TFEB, LINC00612 and miR-31-5p on tumor growth. Western blotting showed high expression of TFEB in HK-2-TFEB and Caki-2-TFEB cells compared to their respective control cells. qRT-PCR revealed enhanced expression of LINC00612, decreased miR-31-5p expression and increased expression of CTNNB1 in HK-2-TFEB and Caki-2-TFEB cells. Dual-luciferase reporter and ChIP experiments confirmed that TFEB specifically bound to the promoter of LINC00612. LINC00612 overexpression in HK-2 cells enhanced cell proliferative capacity, migratory activity, and invasive potential, while its knockdown in HK-2-TFEB cells suppressed these cellular processes. LINC00612 was shown to have targeted binding to miR-31-5p, and miR-31-5p was verified to target CTNNB1. In vivo experiments demonstrated that either TFEB or LINC00612 overexpression promoted tumor growth, whereas overexpression of miR-31-5p inhibited tumor growth. Our findings suggested that overexpression of TFEB upregulated LINC00612 expression and LINC00612 competitively inhibited miR-31-5p, which directly targeted the downstream gene CTNNB1, ultimately promoting tumor progression. TFEB/LINC00612/miR-31-5p axis may be a new molecular therapeutic target for t(6;11) translocation RCC patients.