Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.

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.

The transforming growth factor-β (TGF-β) signaling pathway is believed to contribute to carcinoma development by increasing cell invasiveness and metastasis and inducing the epithelial-to-mesenchymal transition (EMT). Protein phosphatase PPM1A has been reported to dephosphorylate TGF-β-activated Smad2/3, thus inhibiting the TGF-β signaling pathway. In this study, we investigated the role of PPM1A in bladder cancer. PPM1A protein expression was analyzed in 145 bladder cancer specimens. The loss of PPM1A expression was predictive of poor survival and high muscle-invasiveness. PPM1A was more commonly deficient among muscle-invasive relapse samples compared to primary tumors in twenty paired bladder cancer tissues. Functional studies indicated that blockade of PPM1A through lentivirus-mediated RNA interference significantly promoted urinary bladder cancer (BCa) cell motility, the EMT in vitro and metastasis in vivo, and these effects were dependent on the TGF-β/Smad signaling pathway. The increase in p-Smad2/3 induced by TGF-β1 correlated with the degree of PPM1A depletion in BCa cells, which resulted in an altered expression profile of TGF-β-inducible genes. The correlations between PPM1A and biomarkers related to the TGF-β signaling pathway and tumor invasion were also detected in BCa samples. These results demonstrate that loss of PPM1A is associated with the development of tumor invasion in bladder cancer.

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contributed equally to this study.What's known on the subject? and What does the study add?• Thulium laser is a new generation of surgical laser. It is a minimally invasive technology with several advantages, including rapid vaporization and minimal tissue damage and bleeding. However, details regarding the safety and efficacy of thulium laser in treating BPH remains unknown.• We performed a comparative study in 100 patients with BPH of the safety and efficacy of thulium laser resection of the prostate (TMLRP, n = 50) and bipolar transurethral plasmakinetic prostatectomy (TUPKP, n = 50). We found that the efficacy and indications were the same in TMLRP and TUPKP. In TUPKP, the morbidity of urethrostenosis was low, and was nearly bloodless in surgery and had higher safety. Nevertheless, TUPKP is more suitable for patients with larger prostate volume. Objective• To compare the safety and short-term efficacy of thulium laser resection of the prostate (TMLRP) and bipolar transurethral plasmakinetic prostatectomy (TUPKP) for the treatment of patients with benign prostatic hyperplasia (BPH). Methods• A total of l00 patients diagnosed with BPH were randomly divided into two groups, treated with either TMLRP (50, group 1) or TUPKP (50, group 2). • There was no significant difference in preoperative variables such as age, prostate volume, prostate-specific antigen (PSA) level, International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and postvoid residual urine volume (PVR) between the two groups.• The perioperative parameters and therapeutic effects were recorded and compared between the two groups. Results• There were significant differences in the following parameters between the two groups (TMLRP vs TUPKP • At 1 month after the operation, there were four cases of urethral stricture in the TUPKP group.• At 3 months after the operation, IPSS, quality of life (QoL), Qmax and PVR were significantly improved, with no significant difference between the two groups. Conclusions• TMLRP is superior to TUPKP in terms of safety, blood loss, recovery time and complication rate, and is as efficacious as TUPKP for treating BPH.• Operation duration was significantly longer in the TMLRP group than in the TUPKP group.

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.

Our findings suggest that regular, especially long-time regular aspirin use may reduce the risk of overall and advanced prostate cancer. Considering the limitation of included studies, further well-designed large-scaled cohort studies and RCTs are required to draw more definitive conclusions.