Knockdown of long noncoding RNA DLEU1 suppresses the progression of renal cell carcinoma by downregulating the Akt pathway

Abstract

Increasing evidence has indicated that long noncoding RNA s (lncRNA s) are involved in the tumorigenesis and progression of various types of cancer. The lncRNA deleted in lymphocytic leukemia 1 (DLEU 1) has been reported to be dysregulated in cancer cells and thus associated with tumor development; however, the role of DLEU 1 in renal cell carcinoma (RCC) remains unclear. In the present study, DLEU 1 was knocked down using small interfering RNA in the RCC cell lines KETR3 and 786-O to determine the role of DLEU 1. Cell Counting Kit-8, colony formation, Transwell and flow cytometry assays were performed to assess the effects of DLEU 1 on cell proliferation, migration, invasion and apoptosis in KETR3 and 786-O cells. The protein expression levels of factors associated with apoptosis and epithelial-mesenchymal transition (EMT) were examined by western blot. The results demonstrated that silencing DLEU 1 decreased the growth capacity, migration and invasion of KETR3 and 786-O cells. Additionally, loss of DLEU 1 was observed to stimulate the mitochondrial pathway of cell apoptosis via regulation of the expression of Bcl-2/Bax, cleaved caspase-3 and cleaved caspase-9 in KETR3 and 786-O cells. Furthermore, DLEU 1 knockdown significantly inhibited the protein kinase B (Akt) pathway by downregulating the expression of phosphorylated-A kt, cyclin D1 and P70S6 kinase. In addition, depletion of DLEU 1 was observed to impair the process of EMT in RCC cells via the upregulation of E- cadherin, and downregulation of N- cadherin and vimentin. Collectively, these results indicated a pro-oncogenic role of DLEU 1 in the progression and development of RCC via modulation of the Akt pathway and EMT phenotype.