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

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are involved in the tumorigenesis and progression of various types of cancer. The lncRNA deleted in lymphocytic leukemia 1 (DLEU1) has been reported to be dysregulated in cancer cells and thus associated with tumor development; however, the role of DLEU1 in renal cell carcinoma (RCC) remains unclear. In the present study, DLEU1 was knocked down using small interfering RNA in the RCC cell lines KETR3 and 786‑O to determine the role of DLEU1. Cell Counting Kit‑8, colony formation, Transwell and flow cytometry assays were performed to assess the effects of DLEU1 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 DLEU1 decreased the growth capacity, migration and invasion of KETR3 and 786‑O cells. Additionally, loss of DLEU1 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, DLEU1 knockdown significantly inhibited the protein kinase B (Akt) pathway by downregulating the expression of phosphorylated‑Akt, cyclin  D1 and P70S6 kinase. In addition, depletion of DLEU1 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 DLEU1 in the progression and development of RCC via modulation of the Akt pathway and EMT phenotype.

Molecular medicine reports. 2019 Sep 25 [Epub]

Genquan Yue, Caixia Chen, Ligang Bai, Guoqiang Wang, Yong Huang, Yunbin Wang, Hongwei Cui, Yunfeng Xiao

Department of Urology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010000, P.R. China., Clinical Medical Research Center, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010000, P.R. China., The Center for New Drug Safety Evaluation and Research of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, P.R. China.