Circ_0008717 promotes renal cell carcinoma progression by upregulating FBXO17 via targeting miR-217.

BACKGROUND: Renal cell carcinoma (RCC) is a common lethal urological malignancy. Circular RNAs are assumed to play important roles in cancer development. The objective of the present study was to investigate the role and action mechanism of circ_0008717 in RCC. METHODS: The expression of circ_0008717, miR-217 and F-box protein 17 (FBXO17) mRNA was detected by a real-time quantitative polymerase chain reaction. Cell proliferation was examined using a cell counting kit-8 assay and an 5-ethynyl-2'-deoxyuridine assay. Cell apoptosis was assessed by a flow cytometry assay. Cell migration and cell invasion were investigated using a transwell assay. Glycolysis progression was assessed according to the levels of glucose uptake and lactate production. The expression of glycolysis-related proteins and FBXO17 protein was quantified by western blotting. The targets were analyzed by the bioinformatics tools (starBase and circinteractome) and validated by a dual-luciferase reporter assay, RNA pull-down assay and RNA immunoprecipitation assay. A xenograft model was established to monitor the role of circ_0008717 in vivo. RESULTS: Circ_0008717 was upregulated in RCC tissues and cells. Silencing circ_0008717 suppressed RCC cell proliferation, migration, invasion and glycolysis but promoted cell apoptosis. MiR-217 was a target of circ_0008717 and bound to the FBXO17 3' untranslated region. The expression of FBXO17 was positively regulated by circ_0008717 but impaired by miR-217 reintroduction. The inhibitory effects of circ_0008717 knockdown on RCC cell malignant behaviors were reversed by miR-217 inhibition or FBXO17 overexpression. Circ_0008717 knockdown inhibited tumor growth in vivo by regulating miR-217 and FBXO17. CONCLUSIONS: Circ_0008717 aggravated the progression of RCC by activating FBXO17 through targeting miR-217, which provided a novel mechanism for circ_0008717 to participate in RCC progression.

MicroRNA-150-5p-mediated Inhibition of Cell Proliferation, G1/S Transition, and Migration in Bladder Cancer through Targeting NEDD4-binding Protein 2-like 1 Gene.

MicroRNA-150-5p (miR-150-5p) has been implicated in the progression of several cancer types, yet its specific functional role and regulatory mechanisms in bladder cancer (BC) remain largely unexplored. Our study revealed significant downregulation of miR-150-5p and upregulation of NEDD4-binding protein 2-like 1 gene (N4BP2L1) in BC tissues compared to controls using quantitative real-time polymerase chain reaction and western blot analysis, respectively. Reduced miR-150-5p expression correlated with advanced tumor stage and lymph node metastasis, while increased N4BP2L1 levels were associated with larger tumor size by the Chi-square test. Functionally, miR-150-5p exerted significant inhibitory effects on BC cell proliferation, migration, inducing G0/G1 phase arrest, and apoptosis. We confirmed N4BP2L1 as a direct target of miR-150-5p in BC cells using luciferase reporter assay. Crucially, N4BP2L1 knockdown mimicked, while overexpression counteracted the inhibitory impacts of miR-150-5p on BC cell proliferation, migration, and invasion. In addition, N4BP2L1 overexpression reversed miR-150-5p-induced alterations in CDK4, Cyclin D1, Bcl-2, PCNA, Ki-67, N-cadherin, Bad, and E-cadherin levels in BC cells. Based on these results, it can be inferred that the miR-150-5p/N4BP2L1 axis might constitute a promising candidate for therapeutic targeting in the treatment of BC.

Associations between D3R expression in synovial mast cells and disease activity and oxidant status in patients with rheumatoid arthritis.

Dopamine D3 receptor (D3R) on immune cells is involved in the pathogenesis of rheumatoid arthritis (RA). Mast cells (MCs) are currently identified as important effector cells in synovial inflammation of RA, but little is known about the role of D3R on synovial MCs in the pathogenesis of RA. Several inflammatory cells in the synovium induce reactive oxygen species (ROS) formation which are involved in the progression of RA. However, it is unclear whether D3R on synovial MCs is related to the levels of ROS in RA patients. In this study, a total of 73 patients with RA were divided into three groups according to disease activity DAS28 scores. The number of cases in group 1, group 2, and group 3 was 19, 26, and 28, respectively. We examined D3R-positive MC numbers in the synovial fluid and ROS levels in each group of RA patients, and we also analyzed the association of D3R-positive MC numbers with RA disease activity and ROS levels. MDA and protein carbonylation in the serum and synovial fluid were measured to reflect the level of lipid peroxidation and protein oxidation, respectively. Additionally, superoxide dismutase (SOD) and catalase (CAT) in the serum and synovial fluid were used to be markers of antioxidant levels. Our results showed that D3R-positive MCs in the synovial fluid showed a declining trend with the increased disease activity DAS28 score in RA patients. There was negative correlation between D3R-positive MC numbers in the synovial fluid and disease severity DAS28 score of RA patients. Moreover, D3R-positive MC numbers in the synovial fluid were negatively correlated with the level of MDA and protein carbonylation while were positively correlated with antioxidant levels such as SOD and CAT in RA patients. Our results suggested that D3R on MCs may be involved in ROS-mediated pathogenesis of RA.

Protective effects of grape seed extract fractions with different degrees of polymerisation on blood glucose, lipids and hepatic oxidative stress in diabetic rats.

The purpose of this study was to evaluate the effect of grape seed procyanidin (GSPE) fractions with different degrees of polymerisation (DPs) on blood glucose, lipids and hepatic oxidative stress in diabetic rats. Diabetic rats received a daily oral supplement of GSPE with different DPs for 6 weeks. During this period, blood glucose, body weight and food intake were assessed weekly. At the end of the experiment, serum lipid and hepatic oxidative stress were assessed compared with those of rats that did not receive GSPE. GSPE significantly decreased blood glucose, serum lipids and hepatic oxidative stress. Moreover, these effects were significantly better in the groups administered the oligomeric rather than the polymeric forms. These results demonstrate that GSPE has a positive effect on diabetes in rats, and the oligomeric form of GSPE may be more protective than other forms.