Background FGFR3 plays an important role in the development of bladder cancer (BCa). Hsa_circ_0068871 is a circRNA generated from several exons of FGFR3. However, the potential functional role of hsa_circ_0068871 in BCa remains largely unknown. Here we aim to evaluate the role of hsa_circ_0068871 in BCa. Methods We selected miR-181a-5p as the potential target miRNA of hsa_circ_0068871. The expression levels of hsa_circ_0068871 and miR-181a-5p were examined in BCa tissues and paired adjacent normal tissues by quantitative real-time PCR. To characterize the function of hsa_circ_0068871, BCa cell lines were stably infected with lentivirus targeting hsa_circ_0068871, followed by examinations of cell proliferation, migration and apoptosis. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0068871 in BCa. Biotinylated RNA probe pull-down assay, fluorescence in situ hybridization and luciferase reporter assay were conducted to confirm the relationship between hsa_circ_0068871, miR-181a-5p and FGFR3. Results Hsa_circ_0068871 is over-expressed in BCa tissues and cell lines, whereas miR-181a-5p expression is repressed. Depletion of has_circ_0068871 or upregulation of miR-181a-5p inhibited the proliferation and migration of BCa cells in vitro and in vivo. Mechanistically, hsa_circ_0068871 upregulated FGFR3 expression and activated STAT3 by targeting miR-181a-5p to promote BCa progression. Conclusions Hsa_circ_0068871 regulates the miR-181a-5p/FGFR3 axis and activates STAT3 to promote BCa progression, and it may serve as a potential biomarker. Electronic supplementary material The online version of this article (10.1186/s13046-019-1136-9) contains supplementary material, which is available to authorized users.
Aim: Our aim was to analyze the clinicopathological features of lung, liver, bone and brain metastasis in patients with endometrial cancer (EC). Patients & methods: We screened patients diagnosed with EC between 2010 and 2015 from the Surveillance, Epidemiology and End Results database. Results: Among 69,027 eligible EC patients, lung metastasis was the most common. Patients with lung or liver metastasis were at higher risk of bone and brain metastases than those without lung and liver metastasis. Brain metastasis has the lowest survival time (5.0 months) in single organ metastasis. Liver and brain metastasis have the highest death rate in two organ metastasis, and lung, liver and brain metastasis had the lowest survival time (1.0 month) in multi-sites metastasis. Conclusion: Lung metastasis was the most common in EC patients. Assessing distant organ metastasis may help clinicians to determine appropriate follow-up strategy for patients with EC.
Acute kidney injury (AKI) is a serious renal dysfunction syndromes, which predominantly correlates with the excess production of endogenous reactive oxygen/nitrogen species (RO/NSs), triggering a series of pathological processes including cellular apoptosis, renal fibrosis, and ferroptosis. Ferroptosis as an iron‐dependent nonapoptotic regulated cell death is extensively involved in renal damage. Herein, the authors report the engineering of ultrasmall KCa(H2O)2[FeIII(CN)6]·H2O nanoparticles as multienzyme mimetics, termed as CaPB nanozymes, for effectively scavenging RO/NSs and further inhibiting ferroptosis for the treatment of AKI. CaPB nanoparticles can effectively mimic the activity of multienzymes including superoxide dismutase, catalase, peroxidase, and glutathione peroxidase. Furthermore, CaPB nanozymes serving as a robust ferroptosis inhibitor significantly increase the expression of ferroptosis regulator glutathione peroxidase 4 in vitro. Furthermore, the renal accumulation of CaPB nanozymes effectively protects the kidney from oxidative injury and alleviated ferroptosis after intravenous administration. Additionally, the abnormal expression of inflammatory factors is further inhibited by CaPB nanozymes. The results demonstrate that the engineered ultrasmall CaPB nanozyme as a multienzyme mimetic features high potential for RO/NSs scavenging and treating AKI via inhibiting ferroptosis, which promises the clinical translation on the treatment of AKI and other RO/NSs‐related renal diseases.
Purpose : We aimed to reveal the effects of marital status on survival outcomes in patients with penile cancer. Methods : Patients with penile cancer who were diagnosed between 2004 and 2015 were identified by using the Surveillance, Epidemiology and End Results (SEER) database. Kaplan-Meier and Cox regressions were used to analyse the effects of marital status on overall survival (OS) and cancer-specific survival (CSS). Results : Among 3,195 eligible patients with penile cancer, 1,951 (61.1%) patients were married, 365 (11.4%) were divorced or separated, 327 (10.2%) were widowed and 552 (17.3%) were single. The widowed patients had the worst OS median survival time (22 months) and CSS median survival time (23.5 months). Marital status was an independent prognostic factor for OS and CSS of penile cancer patients. The multivariate Cox regression showed that widowed patients exhibited the poorest OS (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.48-2.03, p < 0.001) and the poorest CSS (HR: 1.64; 95% CI: 1.144-1.279, p < 0.001) compared with married patients. Similar results were observed in our centre database and the subgroup analyses based on the SEER stage and grade. Conclusions : In our study, we found that marital status was an independent prognostic factor for survival in patients with penile cancer. Additionally, widowed patients had the lowest OS and CSS compared with married patients.
Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, CDC5L was also found to act as a candidate oncogene in osteosarcoma and cervical tumours. However, the role of CDC5L expression in bladder cancer remains unclear. Here, we analysed the expression and clinical significance of CDC5L in bladder cancer tissues. The expression of CDC5L in fresh bladder cancer tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in bladder cancer. The expression of CDC5L was significantly associated with bladder cancer pathology grade and Ki67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for the survival of bladder cancer patients. To determine whether CDC5L could regulate the proliferation of bladder cancer cells, we transfected bladder cancer cells with an interfering RNA targeting CDC5L and then investigated cell proliferation with a cell counting kit (CCK)-8, flow cytometry assays, colony formation and xenograft assay analyses. Our results indicate that knockdown of CDC5L inhibits proliferation of bladder cancer cells. In addition, reduced expression of CDC5L induced apoptosis of bladder cancer cells and inhibited their migration, invasion and EMT. These findings suggest that CDC5L might play an important role in bladder cancer and thus be a promising therapeutic target of bladder cancer.
Background: Serum cystatin C (CysC) is still becoming used as a marker of renal function but is far from being commonly used worldwide. The purpose of this study was to characterize the ureteral calculi patients with hydronephrosis-caused CysC changes in renal function. Methods: To better reflect the changes of renal function, we constructed models of ureteral obstruction in rats to mimic the hydronephrosis caused by human ureteral calculi. Moreover, our study included 200 patients diagnosed with ureteral calculi in our hospital between June 2017 and 2018. We compared the estimated glomerular filtration rate using different equations based on CysC and/or serum creatinine (SCr). Results: We found that the expression of CysC and SCr increased with the prolonged obstruction time by enzyme linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry further demonstrated that the expression of CysC increases with the degree of hydronephrosis. Among 200 patients with ureteral calculi, 40 (20.0%) had no hydronephrosis, 110 (55.0%) had mild hydronephrosis, 32 (16.0%) had moderate hydronephrosis and 18 (9.0%) had severe hydronephrosis. As the degree of hydronephrosis increased, the expression of neutrophil percentage, CysC, blood urea nitrogen, SCr and serum uric acid also increased. Multivariate analyses demonstrated that only CysC was an independent risk factor for hydronephrosis (p = 0.003). In addition, CysC and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) CysC equation showed the highest veracity in renal function estimation of patients with hydronephrosis caused by ureteral calculus. Conclusion: For patients with hydronephrosis caused by ureteral calculi, CysC better reflects the changes in renal function, and the CKD-EPI CysC equation has the highest accuracy.
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