No abstract

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.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) modulates T helper cell differentiation and nuclear factor-κB (NF-κB) pathway-mediated inflammation and potentially regulates lipid metabolism, which are all critical factors involved in atherosclerosis. The present study aimed to investigate the effect of MALT1 on the cellular functions of proatherogenic vascular smooth muscle cells (VSMCs). Therefore, to establish a human proatherogenic VSMC model, VSMCs were treated with different doses of oxidized low-density lipoprotein (oxLDL). Subsequently, the effect of MALT1 overexpression or knockdown in proatherogenic VSMCs treated with or without NF-κB activator was also explored. The results showed that treatment of proatherogenic VSMCs with oxLDL significantly elevated the mRNA and protein expression levels of MALT1 in a dose-dependent manner. Furthermore, MALT1 overexpression enhanced cell viability, invasion and phenotype switching and reduced apoptosis in proatherogenic VSMCs. However, MALT1 knockdown exerted the opposite effect on the above cellular functions. Additionally, the results revealed that MALT1 could positively regulate the NF-κB pathway in proatherogenic VSMCs. Moreover, treatment of proatherogenic VSMCs with NF-κB activator not only exacerbated the dysregulation of cellular functions, but also hampered the effect of MALT1 knockdown on attenuating cell growth, invasion and synthetic phenotype switching, thus suggesting that NF-κB was essential for the regulation of MALT1-triggered functions in proatherogenic VSMCs. In conclusion, the current study suggested that MALT1 could exacerbate cell viability, mobility and synthetic phenotype switching of proatherogenic VSMCs in a NF-κB signaling-dependent manner. Therefore, MALT1 could be considered as a potential therapeutic target for atherosclerosis.