EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway.

Prostate cancer (PCa) represents a substantial global health concern and a prominent contributor to male cancer-related mortality. The aim of this study is to explore the role of B-type endothelin receptor (EDNRB) in PCa and evaluate its therapeutic potential. The investigation employed predictive methodologies encompassing data acquisition from the GEO and TCGA databases, gene screening, enrichment analysis, in vitro experiments involving PCR, Western blotting, wound healing, and Transwell assays, as well as animal experiments. Analysis revealed a significant downregulation of EDNRB expression in PCa cells. Overexpression of EDNRB demonstrated inhibitory effects on tumor cell growth, migration, and invasion, likely mediated through activation of the cGMP-Protein Kinase G pathway. In vivo experiments further confirmed the tumor-suppressive properties of EDNRB overexpression. These findings underscore the prospect of EDNRB as a therapeutic target for PCa, offering novel avenues for PCa treatment strategies.

MiR-141-3p promotes malignant progression in prostate cancer through AlkB homolog 5-mediated m6A modification of protein arginine methyltransferase 6.

Prostate cancer (PCa) is one of the leading causes of cancer-related death in males worldwide and exploring more reliable biomarkers for PCa is essential for the diagnosis and therapeutics for the disease. Although the functions of miR-141-3p and AlkB homolog 5 (ALKBH5) were identified in some cancers, whether they were involved in the development of PCa remains unclear. In this study, reverse transcription-quantitative polymerase chain reaction unveiled that the expression of ALKBH5 was reduced in PCa tissues and was negatively correlated with miR-141-3p. ALKBH5 attenuated the malignant development of PCa through suppressing the growth, migration, invasion, and sphere formation abilities of PCa cells. In addition, the luciferase activity assay identified that ALKBH5 was corroborated as a downstream target of miR-141-3p. Moreover, miR-141-3p expression was boosted in PCa tissues and cells and inhibition of miR-141-3p suppressed the tumor growth of PCa in vivo. Moreover, ALKBH5 was confirmed to suppress protein arginine methyltransferase 6 (PRMT6) expression through N6-methyladenosine (m6A) modification. We further identified that miR-141-3p-modulated PRMT6 level through mediating ALKBH5. Furthermore, PRMT6 level was positively correlated with miR-141-3p level and negatively associated with ALKBH5 level. Finally, rescue assays also uncovered that miR-141-3p aggravated PCa development by regulating PRMT6. In conclusion, miR-141-3p accelerated the malignant progression of PCa through ALKBH5-mediated m6A modification of PRMT6, which might offer a novel insight into the role of miR-141-3p and ALKBH5 in the treatments of PCa patients.

Comparison of super-mini-PCNL and flexible ureteroscopy for the management of upper urinary tract calculus (1-2 cm) in children.

OBJECTIVES: To retrospectively evaluate the efficacy and safety of super-mini percutaneous nephrolithotomy (SMP) and retrograde intrarenal surgery (RIRS) for children with upper urinary tract calculus (1-2 cm). PATIENTS AND METHODS: Children with upper urinary tract calculus (1-2 cm) who underwent the SMP or RIRS were enrolled in this study. Patients were divided into two groups: group SMP, 36 patients; and group RIRS, 25 patients. Patients were evaluated with KUB radiography or CT after 1 month. The collected data were analyzed. RESULTS: The mean stone size was 14.18 mm in group SMP, and 14.00 mm in group RIRS (p = 0.812). Group RIRS compared to group SMP showed longer operating time [76.3 vs 53.9 min (p = 0.002)], and postoperative hospital stay [4.2 vs 2.9 days (p = 0.011)]. The overall stone-free rate (SFR) was 94.4% for group SMP, and 60.0% for group RIRS in 1 month after operation (p = 0.001). The re-treatment rate was significantly higher in group RIRS compared to group SMP [20.0% vs 0.0% (p = 0.009)]. The complication rate was 5.6%, and 24.0% for groups SMP, and RIRS, respectively (p = 0.036). CONCLUSIONS: SMP was more effective than RIRS to obtain a better SFR, less re-treatment rate, and complication rate in children with upper urinary tract calculus (1-2 cm).

Construction and Validation of a Robust Cancer Stem Cell-Associated Gene Set-Based Signature to Predict Early Biochemical Recurrence in Prostate Cancer.

BACKGROUND: Postoperative early biochemical recurrence (BCR) was an essential indicator for recurrence and distant metastasis of prostate cancer (PCa). The aim of this study was to construct a cancer stem cell- (CSC-) associated gene set-based signature to identify a subgroup of PCa patients who are at high risk of early BCR. METHODS: The PCa dataset from The Cancer Genome Atlas (TCGA) was randomly separated into discovery and validation set. Patients in discovery set were divided into early BCR group and long-term survival group. Propensity score matching analysis and differentially expressed gene selection were used to identify candidate CSC-associated genes. The LASSO Cox regression model was finally performed to filter the most useful prognostic CSC-associated genes for predicting early BCR. RESULTS: By applying the LASSO Cox regression model, we built a thirteen-CSC-associated gene-based early BCR-predicting signature. In the discovery set, patients in high-risk group showed significantly poorer BCR free survival than that patients in low-risk group (HR: 4.91, 95% CI: 2.75-8.76, P < 0.001). The results were further validated in the internal validation set (HR: 2.99, 95% CI: 1.34-6.70, P = 0.005). Time-dependent ROC at 1 year suggested that the CSC gene signature (AUC = 0.800) possessed better predictive value than any other clinicopathological features in the entire TCGA cohort. Additionally, survival decision curve analysis revealed a considerable clinical usefulness of the CSC gene signature. CONCLUSIONS: We successfully developed a CSC-associated gene set-based signature that can accurately predict early BCR in PCa cancer.

Alteration of Androgen Receptor Protein Stability by Triptolide in LNCaP Cells.

Background and Objective: Although triptolide was effective for prostate cancer (PCa), the mechanism is still unclear. Androgen receptor (AR) plays a large role in the development and progression of PCa, even after castration. The present study aimed at investigating the effects of triptolide on AR protein stability and the possible mechanism. Materials and Methods: By blocking protein synthesis with cycloheximide (CHX), the effect of triptolide on AR protein stability was investigated with western blot assay. The potential role of calpains in triptolide reduced AR protein stability was investigated with calpain inhibitor and Ca2+ chelator. Results: Triptolide down-regulated AR protein level when protein synthesis was blocked by CHX, demonstrating the decrease of AR protein stability. The AR protein level was restored when the cells were co-treated with triptolide and calpain inhibitor or Ca2+ chelator, indicating the important role of calpains. Conclusions: The results indicate that triptolide can activate calpain via promoting intracellular Ca2+ accumulation, and thus decrease the stability of AR protein, subsequently resulting in the breakdown of the AR protein in LNCaP cells. This work provides an experimental basis and evidence to elucidate the anti-PCa mechanisms of triptolide.

Comparison of the protein expression of calpain-1, calpain-2, calpastatin and calmodulin between gastric cancer and normal gastric mucosa.

The understanding of molecular mechanisms that are involved in the development and the progression of gastric cancer (GC) are of importance for the diagnosis and treatment. The calpain system, which contains the calpains and the endogenous inhibitor, has been suggested as an important factor in the tumorigenesis and migration of colorectal adenocarcinoma, breast and ovarian cancer, and as a prognostic marker for GC. However, the expression level of calpain system proteins in GC and normal-appearing peritumoral gastric mucosa remain unknown. The present study investigated the expression of calpain-1 (CAPN1), calpain-2 (CAPN2), calpastatin and calmodulin (CaM) in GC and uninvolved gastric mucosa tissues with immunohistochemistry. Results demonstrated that CAPN2 protein level increased in GCs compared with normal tissues, while calpastatin and CaM protein level decreased. No evident alterations were observed for CAPN1. Although the protein expression of all these four proteins was not in association with the clinical variables of GC in the present study, higher calpain enzyme activity could be a negative prognostic marker, since calpains are responsible for the generation of active forms of certain proteins that facilitate the progression of cancer. The ratio of (CAPN1 × CAPN2)/(calpastatin × CaM) may serve as a potential index for diagnosis of GC.

Identification of TMPRSS2-ERG mechanisms in prostate cancer invasiveness: Involvement of MMP-9 and plexin B1.

The relationship of TMPRSS2-ERG fusion gene with matrix metalloproteinase-9 (MMP-9) and PLXNB1 (plexin B1) in regulation of prostate cancer (PCa) aggressiveness was investigated. Fluorescence in situ hybridization (FISH) assays, qRT-PCR and western blot analysis were employed to detect the expression of TMPRSS2-ERG fusion gene, ERG, MMP-9 and PLXNB1 of 135 human tissues, which included 55 metastatic PCa cases, 50 localized PCa cases and 30 BPH cases. Then using siRNA (anti-ERG, MMP-9 and PLXNB1, respectively) downregulation of the target gene of VCaP and PC-3 cells, MTT and Transwell were performed. The results showed that the positive rate of TMPRSS2-ERG fusion was 38.1% (40/105) in total PCa samples, 47.3% (26/55) of metastatic PCa, 28.0% (14/50) of localized PCa, while 0.0% (0/30) in BPH samples. The mRNA and protein expression of ERG, MMP-9 and PLXNB1 were higher in metastatic PCa (P<0.0001), and the mRNA expression of the three genes were positively correlated with TMPRSS2-ERG fusionin PCa group (P<0.0001). siRNA transfected PCa cells can effectively downregulate the target gene expression, and we identified that MMP-9 and PLXNB1 expression were all regulated by TMPRSS2-ERG fusion gene. While only PLXNB1 contributed to TMPRSS2-ERG mediated enhancements of VCaP cell migration and invasion. The results demonstrated that PLXNB1, but not MMP-9, was the target gene directly related to TMPRSS2-ERG in PCa cell migration and invasion.

Effect of prostate volume on the peripheral nerve block anesthesia in the prostate biopsy: A strobe-compliant study.

OBJECTIVE: The objective of this study was to evaluate the anesthetic efficacy of periprostatic nerve block (PNB) in transrectal ultrasound (TRUS)-guided biopsy on different prostate volume. METHODS: A total of 568 patients received prostate biopsy in our hospital from May 2013 to September 2015 and were retrospectively studied. All patients were divided into local anesthesia group (LAG) and nerve block group (NBG). Then each group was subdivided into 4 subgroups (20-40, 40-60, 60-100, and >100 mL groups) according to different prostate volume range. Visual analogue scale (VAS) and visual numeric scale (VNS) were used to assess the patient's pain and quantify their satisfaction. The scores and complications were compared between the groups. RESULTS: The age and serum prostate-specific antigen (PSA) level before biopsy had no significant differences at intergroup or intragroup level. The VAS scores were significantly lower in the NBG than those in the LAG in terms of prostate volume (1 (1-2) versus 2 (1-3), 2 (1-3) versus 2 (2-4), 2 (2-3) versus 3 (2-5), 4 (3-5) versus 5 (4-7), all P < 0.05). Conversely, the VNS scores were higher in the NBG (4 (3-4) versus 3.5 (3-4), 3 (3-4) versus 3 (3-3), 3 (2-4) versus 3 (2-3), 2 (2-2) versus 1 (1-2), all P < 0.05). Patients with smaller prostate volume undergoing PNB or local anesthesia experienced significantly lower pain and higher satisfaction scores than those with large prostate. Whether in PNB or local anesthesia group, patients with large prostate volume had more chance to have hematuria, hemospermia, urinary retention than smaller one except infection (P < 0.05). Those complications had no significant differences between LAG and NBG (P > 0.05). CONCLUSION: Compared with local anesthesia, ultrasound-guided PNB has superior analgesic effect and equal safety, but for patients with a large prostate volume, the analgesic effect is inefficient.

[Effects of triptolide on the expression of androgen receptor in human prostate LNCaP cells and its mechanism of action].

To study the regulation of androgen receptor (AR) expression in human prostate cancer LNCaP cells by triptolide (TP) and the possible mechanism, by using qRT-PCR and Western blot, the AR mRNA and protein levels in TP treated LNCaP cells were detected, and the AR protein level in TP and NF-κB inhibitor treated LNCaP cells was also detected; a series of pGL3-AR promoter reporter gene vectors were built using restriction-free cloning method, and the vectors were employed to investigate the effects of TP on the transcriptional activity of AR promoter in LNCaP cells; the upstream proteins which may play regulatory roles were detected using western blot assay. After treated LNCaP cells with TP for 48 h, AR mRNA and protein expressions decreased with increasing TP concentration. The expression of AR target gene PART1 and prostate specific antigen (PSA) was also downregulated by TP treatment; a series of pGL3-AR promoter reporter vectors were constructed and validated by sequencing and luciferase activity; the results of dual luciferase reporter assay showed that TP downregulated AR at the transcriptional level; PI3K/AKT/NF-κB pathway which is associated with AR promoter activity was drowregulated by TP. In conclusion, our results demonstrated that the transcriptional activity of AR in LNCAP cells was downregulated by TP, and PI3K/AKT/NF-κB pathway may be involved in the regulation mechanism.