Circ-SAR1A Promotes Renal Cell Carcinoma Progression Through miR-382/YBX1 Axis.

BACKGROUND: Accumulating evidence points to a role for circular RNAs (circRNAs) in important regulatory function in tumor advancement. We explored the effect and function of circ-SAR1A in renal cell carcinoma (RCC). METHODS: circ-SAR1A expression in RCC tissues and cell lines was explored by qRT-PCR. The roles of circ-SAR1A on RCC progression were explored by in vitro function assays. Moreover, we determined the underlying mechanism of circ-SAR1A in RCC progression through bioinformatics analysis and dual-luciferase reporter assays. RESULTS: Our data reveal that circ-SAR1A is significantly high in RCC tissues and cell lines. High circ-SAR1A levels are correlated to advanced Fuhrman grade, and lymph-node metastasis in RCC patients. Functional experiments indicate that circ-SAR1A suppression decreased RCC cell growth and invasion abilities in vitro. Mechanistically, circ-SAR1A upregulated YBX1 expression by sponging miR-382, resulting in promoting the growth and invasion in RCC cells. CONCLUSION: Our data indicate that the circ-SAR1A/miR-382/YBX1 axis plays a critical role in RCC progression, which serve as a potential novel treatment strategy of RCC.

Preoperative predictors of early death risk in bladder cancer patients treated with robot-assisted radical cystectomy.

BACKGROUND: Early identification of early death for bladder cancer patients undergoing radical cystectomy based on the laboratory findings at the time of diagnosis could improve the overall survival. The study aimed to explore preoperative factors associated with higher risk of early death (within 1 year after surgery) for bladder cancer patients. METHODS: A total of 186 bladder cancer patients who underwent robot-assisted radical cystectomy (RARC) were identified between October 2014 and May 2017. The probability of dying within 1 year after RARC was defined as the end point "early death." Predictive factors including clinical features and laboratory findings at diagnosis were retrospectively collected. RESULTS: Median follow-up time after RARC was 20.6 months (1.2-43.7 months). Fifty-one patients (27.4%) died during follow-up and 31 within 1 year from surgery (1-year mortality rate: 16.7%). All potentially prognostic factors were assessed on univariate analyses, which revealed the following factors as being associated with higher risk of early death within 1 year after RARC: older age (P = 0.004), advanced clinical stage (P = 0.005), presence of hydronephrosis (P = 0.021), higher fibrinogen (P = 0.007), higher PLR (P = 0.031), and lower PNI (P = 0.016). In a multivariate Cox proportional hazard regression model analysis, age >60 years (HR = 7.303, 95% CI 1.734-30.764; P = 0.007) and fibrinogen ≥3.295 g/L (HR = 2.396, 95% CI 1.138-5.045; P = 0.007) at diagnosis were independent prognostic factors of early death after RARC. CONCLUSION: Age and preoperative elevated plasma fibrinogen level were independent predictors for 1-year mortality after RARC. We believe that plasma fibrinogen levels may become a useful biomarker, which may help guide the treatment decision-making process for patients with bladder cancer.

Acidosis promotes cell apoptosis through the G protein-coupled receptor 4/CCAAT/enhancer-binding protein homologous protein pathway.

The aim of the present study was to investigate the effects of acidosis on the apoptosis of renal epithelial and endothelial cells, and the molecular pathways responsible for this. A human proximal tubular cell line, HK-2, and human umbilical vein endothelial cells (HUVECs), were transfected with control or G protein-coupled receptor 4 siRNA for 36 h. Cells were exposed to normal (pH 7.4) or acidic (pH 6.4) media. Western blot analysis was used to assess the protein expression levels of G protein-coupled receptor 4 (GPR4), CCAAT/enhancer-binding protein homologous protein (CHOP) and cleaved caspase-3. Cell apoptosis was examined using the TUNEL assay and the lactate dehydrogenase (LDH) release assay. Using these techniques, it was demonstrated that acidosis increased the protein expression levels of GPR4, CHOP, cleaved caspase-3 and intracellular cyclic adenosine monophosphate levels in hypoxia/reoxygenation (HR)-treated cell lines. Knockdown of GPR4 in HK-2 cells and HUVECs markedly reduced the protein expression levels of acidosis-mediated GPR4, CHOP and cleaved caspase-3, as well as the rate of cell apoptosis. Therefore, the results of the present study suggested that acidosis promotes the apoptosis of HK-2 cells and HUVECs by regulating the GPR4/CHOP pathway.

GPR4 knockout improves renal ischemia-reperfusion injury and inhibits apoptosis via suppressing the expression of CHOP.

The aim of the present study was to investigate the effects and molecular mechanisms of GPR4 (G-protein-coupled receptor 4) in cell apoptosis and renal ischemia-reperfusion (IR) injury in vivo and in vitro GPR4-/- mice and wild-type (WT) mice underwent renal IR or sham procedures. For hypoxia/reoxygenation (HR), human umbilical vein endothelial cells (HUVECs) were subjected to 4 h of hypoxia, followed by 6 h of reoxygenation. Renal histological changes were observed by periodic acid-Schiff staining and myeloperoxidase activity. Apoptosis was detected by TUNEL staining. GPR4, C/EBP-homologous protein (CHOP) and cleaved caspase-3 protein expressions were detected by western blot. Both GPR4 and CHOP were up-regulated after renal IR in mice. GPR4-knockout mice had significantly less renal damage and decreased TUNEL-positive cells than WT controls after IR. Bone marrow chimeras demonstrated that it was due to the GPR4 inactivation in renal parenchymal cells. Moreover, GPR4 was mainly expressed in endothelial cells after renal IR. GPR4 knockdown markedly inhibited CHOP expression and cell apoptosis in the HUVECs after HR treatment. GPR4 blockade attenuated renal injury after IR and reduced the cell apoptosis through the suppression of CHOP expression.