The long non-coding RNA PCAL7 promotes prostate cancer by strengthening androgen receptor signaling.

BACKGROUND: The prostate cancer (PCa) has been a global problem to men health. Notably, the androgen receptor (AR) is essential for both normal development of prostate and prostate cancer progression. METHODS: The RNA sequencing was used to identify the novel long non-coding RNA (lncRNA) termed PCAL7. The RT-qPCR was performed to quantify PCAL7 expression. Migration and proliferation assays were used to examine the function of PCAL7. Fluorescence in situ hybridization (FISH) was used to determine subcellular localization. RESULTS: By RNA sequencing, the differentially expressed lncRNAs were identified (top 10 upregulated lncRNAs: PCAL7, AC083843.1, CTC-338M12.3, RP11-443B7.1, RP11-1008C21.2, RN7SL329P, RP4-773N10.4, RP11-264B17.2, KB-1507C5.2, and RP11-20B24.6; top 10 downregulated lncRNAs: RP11-77H9.2, RAB11FIP1P1, AP001625.6, CTA-217C2.1, RP11-603J24.7, RP11-315I20.1, AC092839.1, RP4-758J18.10, RP11-259O2.3, and HMGN2P17). PCAL7 was the lncRNA with the highest fold upregulation and significantly correlated with AR signaling during prostate cancer progression. The AR-regulated PCAL7 was abundantly overexpressed in prostate cancer tissues and AR-dependent cell lines. PCAL7 knockdown inhibited cell migration and proliferation. Consistently, the migration and proliferation were promoted by PCAL7 overexpression. PCAL7 depletion via antisense oligonucleotides (ASOs) markedly suppressed AR signaling and tumor growth. Mechanistically, PCAL7 interacted with Huntingtin-interacting protein 1 (HIP1) to stabilize HIP1. Therefore, PCAL7 could advance AR signaling via a novel positive feedback loop. CONCLUSION: Our experiments support an oncogenic role for PCAL7 which promotes prostate cancer progression suggesting PCAL7 may serve as a potential therapeutic target.

Robotic-assisted laparoscopic artery-sparing varicocelectomy using indocyanine green fluorescence angiography: Initial experience.

We reported our initial experience of robotic-assisted laparoscopic artery-sparing varicocelectomy using indocyanine green (ICG) fluorescence angiography in treatment of varicocele. A total of 45 varicocelectomies in 27 patients were performed. The mean operation time was 49.1 ± 8.5 min for unilateral and 65.6 ± 8.3 min for bilateral repair. 47.2 s after ICG injection, testicular artery (TA) was visualised. After an interval of 31.3 s, fluorescent veins were identified. Of all the 45 spermatic cords, 68.9% had a solitary artery, while 31.1% had 2 arteries. The mean hospital stay was 1.6 ± 0.9 days. Semen concentration and motility were significantly improved 6 months after surgery, no recurrence, hydrocele or testicular atrophy was observed. Our study demonstrated that robotic-assisted laparoscopic artery-sparing varicocelectomy using ICG fluorescence angiography is a safe, effective and promising technique in treatment of varicocele.

A Modified Transurethral Stenting Technique for (Robot-Assisted) Laparoscopic Ureteral Reimplantation.

BACKGROUND: Ureteral stenting is a technique-demanding procedure performed during robot-assisted laparoscopic ureteral reimplantation (RALUR). Many stenting techniques have been reported; however, none of them could be accepted as an ideal way. OBJECTIVES: The aim of the study was to report our initial results of a modified stenting technique for RALUR. METHODS: Consecutive 4 patients undergoing RALUR were prospectively enrolled into our study. Our ureteral stenting technique included the following steps: catheterize a head-cut Foley catheter at the beginning of the operation, drag out the Foley catheter from the ureterovesical stoma after finishing posterior anatomosis, insert a guide wire through the catheter to the ureter lumen, and place the double-J (DJ) stent over the guide wire with a pusher. RESULTS: All surgeries were successfully performed without severe complications. The mean stenting time was 1.6 min. No submucosa pseudocanal was found during stenting. DJ stent was removed 4 weeks after surgery. During the 3-month follow-up, it was observed that no vesicoureteral reflux or ureter stricture was found. CONCLUSIONS: Our ureteral stenting technique is an effective, simple, and safe procedure in RALUR, and could also be performed in laparoscopic ureteral reimplantation.

Lentivirus-Mediated Silencing of Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase 2 Inhibits Release of Inflammatory Cytokines and Apoptosis in Renal Tubular Epithelial Cells Via Inhibition of the TLR4/NF-kB Pathway in Renal Ischemia-Reperfusion Injury.

BACKGROUND/AIMS: Renal reperfusion injury occurs after the blood flow to the ischemic kidney is re-established under various clinical conditions, such as organ transplantation, renal artery stenosis, embolic disease, and the repair of descending aortic. The current study aims to explore the effects of src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) on the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells by regulating the TLR4/NF-κB signaling pathway in rats with renal ischemia-reperfusion (I/R) injury. METHODS: A total of 60 normal clean Sprague Dawley (SD) (WT) rats were used in this study. The levels of creatinine (Cr) and blood urea nitrogen (BUN) were determined using an automatic biochemical analyzer. The apoptosis in renal tissue was detected by TUNEL assay. The renal tubular epithelial cells of rats were cultured, infected and treated with different lentivirus vectors. The serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-1ß and SHP27 were measured. Reverse transcription quantitative polymerases chain reaction and Western blot analysis were performed to measure the expression of relevant genes and proteins. Furthermore, the effect of SHP-2 on the proliferation, cell cycle and apoptosis of renal tubular epithelial cells was also investigated. RESULTS: In the serum of rats with renal I/R injury and prolonged reperfusion time, the contents of Cr and BUN were increased, the positive expression of SHP-2 was higher, the level of apoptosis was promoted, IL-6, TNF-α, IL-1ß and SHP27 expression in the serum was increased, the expression of SHP2, TLR4, NF-κB, IL-6, TNF-α and Bax was up-regulated, and the expression of Bcl-2 was down-regulated. Lentivirus-mediated silencing of SHP-2 promoted the proliferation of renal tubular epithelial cells, inhibited their apoptosis, and reduced the expression of inflammatory factors in these cells by functionally suppressing the TLR4/NF-κB signaling pathway. CONCLUSION: The results indicated that lentivirus-mediated silencing of SHP-2 inhibited the release of inflammatory cytokines and the apoptosis of renal tubular epithelial cells, and promoted the proliferation of these cells by inhibiting the TLR4/NF-κB signaling pathway in rats with renal I/R injury.

Curcumin inhibits bladder cancer progression via regulation of ß-catenin expression.

Bladder cancer has a considerable morbidity and mortality impact with particularly poor prognosis. Curcumin has been recently noticed as a polyphenolic compound separated from turmeric to regulate tumor progression. However, the precise molecular mechanism by which curcumin inhibits the invasion and metastasis of bladder cancer cells is not fully elucidated. In this study, we investigate the effect of curcumin on the bladder cancer as well as possible mechanisms of curcumin. The expression of ß-catenin was detected by quantitative real-time polymerase chain reaction and immunohistochemical analysis in a series of bladder cancer tissues. In addition, bladder cancer cell lines T24 and 5637 cells were treated with different concentrations of curcumin. The cytotoxic effect of curcumin on cell proliferation of T24 and 5637 cells was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The migration and invasion capacity of T24 and 5637 cells were measured by transwell assay. The effects of curcumin on expression levels of ß-catenin and epithelial-mesenchymal transition marker were determined by western blotting. The ß-catenin expression was significantly upregulated in bladder cancer tissues when compared with corresponding peri-tumor tissues. Furthermore, curcumin inhibited the cell proliferation of T24 and 5637 cells, and curcumin reduced the migration and invasive ability of T24 and 5637 cells via regulating ß-catenin expression and reversing epithelial-mesenchymal transition. Curcumin may be a new drug for bladder cancer.

p21 and CK2 interaction-mediated HDAC2 phosphorylation modulates KLF4 acetylation to regulate bladder cancer cell proliferation.

Krüppel-like factor 4 (KLF4) is a transcription factor involved in both tumor suppression and oncogenesis as a transcriptional activator or repressor in a context-dependent manner. KLF4 acts as a regulator of p53 depending on p21 status in breast cancer. However, the mechanisms underlying the distinct role of KLF4 remain poorly understood. Here, we revealed that p21 depletion converted KLF4 from a cell cycle inhibitor to a promoter of bladder cancer cell proliferation. Additionally, KLF4 was acetylated in a p21-dependent manner to inhibit bladder cancer cell growth as a tumor suppressor. However, deacetylated KLF4 functioned as an oncogene promoting bladder cancer cell proliferation. Mechanistically, p21 and CK2 interaction, but not CK2 alone, enhanced HDAC2 phosphorylation and restricted KLF4 deacetylation and subsequent tumor promotion. Furthermore, we observed that KLF4 was acetylated by CBP/p300 and that overexpression of CBP resulted in KLF4 acetylation and tumor suppression even in p21-depleted bladder cancer cells. Moreover, we discovered that Notch-1 knockdown-induced KLF4 is acetylated form of KLF4, which may mediate Notch-1 function in bladder cancer cell proliferation. Our data demonstrate that KLF4 acts as a tumor suppressor or oncogene to activate or repress target gene transcription depending on its acetylation status, which is regulated by p21 and CK2 interaction-mediated HDAC2 phosphorylation. Targeting KLF4 at the post-transcriptional levels may provide novel insight for bladder cancer therapy.

Robot-assisted laparoscopic resection of a huge pelvic tumor: A case report.

The traditional open surgery, for the treatment of huge tumor in the narrow space of pelvic cavity and in close proximity to pelvic organs and neurovascular structures, is very difficult and challenging. We report a case of huge neurilemmoma operated using the robot-assisted laparoscopy. We used interventional pre-operation embolization to control blood supply of tumor because MRI showed the tumor had a sufficient blood supply.

Clinical significance, molecular characterization, and immune microenvironment analysis of coagulation-related genes in clear cell renal cell carcinoma.

Background: Numerous studies have revealed a tight connection between tumor development and the coagulation system. However, the effects of coagulation on the prognosis and tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) remain poorly understood. Methods: We employed the consensus clustering method to characterize distinct molecular subtypes associated with coagulation patterns. Subsequently, we examined variations in the overall survival (OS), genomic profiles, and TME characteristics between these subtypes. To develop a prognostic coagulation-related risk score (CRRS) model, we utilized the least absolute shrinkage and selection operator Cox regression and stepwise multivariate Cox regression analyses. We also created a nomogram to aid in the clinical application of the risk score, evaluating the relationships between the CRRS and the immune microenvironment, responsiveness to immunotherapy, and targeted treatment. The clinical significance of PLAUR and its biological function in ccRCC were also further analyzed. Results: There were significant differences in clinical features, prognostic stratification, genomic variation, and TME characteristics between the two coagulation-related subtypes. We established and validated a CRRS using six coagulation-related genes that can be employed as an effective indicator of risk stratification and prognosis estimation for ccRCC patients. Significant variations in survival outcomes were observed between the high- and low-risk groups. The nomogram was proficient in predicting the 1-, 3-, and 5-year OS. Additionally, the CRRS emerged as a novel tool for evaluating the clinical effectiveness of immunotherapy and targeted treatments in ccRCC. Moreover, we confirmed upregulated PLAUR expression in ccRCC samples that was significantly correlated with poor patient prognosis. PLAUR knockdown notably inhibited ccRCC cell proliferation and migration. Conclusion: Our data suggested that CRRS may be employed as a reliable predictive biomarker that can provide therapeutic benefits for immunotherapy and targeted therapy in ccRCC.

Diagnostic and prognostic potentials of AK126393 in bladder cancer.

PURPOSE: To elucidate the diagnostic and prognostic potentials of lncRNA AK126393 in bladder cancer. METHODS: The expression levels of AK126393 in 60 matched bladder cancer tissues and paracancerous tissues were determined. In addition, AK126393 level in bladder cancer patients with different tumor staging (stage I-II and stage III-IV) was detected as well. Receiver operating characteristic (ROC) was introduced for assessing the diagnostic potential of AK126393 in bladder cancer. Based on the cut-off value of AK126393 in the enrolled 60 bladder cancer patients, they were assigned into high and low expression groups, respectively. Correlation between AK126393 level and pathological indexes of bladder cancer patients was analyzed by chi-square test. By collecting 5-year follow-up data, Kaplan-Meier method was conducted to evaluate survival influenced by AK126393. Moreover, Cox regression model was applied for analyzing potential factors affecting the prognosis of bladder cancer patients. RESULTS: AK126393 was downregulated in bladder cancer tissues than in paracancerous ones. Its level remained lower in bladder cancer patients with stage III-IV relative to those with stage I-II. ROC illustrated the diagnostic potential of AK126393 in bladder cancer (AUC=0.8647, diagnosis threshold=2.03, sensitivity=76.7%, specificity=96.7%, Youden index=0.734). Besides, lower level of AK126393 was observed in bladder cancer patients with stage III-IV, lymph node metastasis or high-level differentiation. Kaplan-Meier curves demonstrated worse prognosis in bladder cancer patients expressing low level of AK126393. Cox regression analysis showed that AK126393 level, TNM staging, lymph node metastasis and tumor differentiation were independent risk factors influencing the prognosis of bladder cancer. CONCLUSIONS: AK126393 is downregulated in bladder cancer and closely linked to high rate of metastasis, advanced stage and poor prognosis. AK126393 may serve as diagnostic and prognostic hallmark in bladder cancer.

Temperature profiles of calyceal irrigation fluids during flexible ureteroscopic Ho:YAG laser lithotripsy.

PURPOSE: To evaluate calyceal irrigation fluid temperature changes during flexible ureteroscopic Ho:YAG laser lithotripsy. METHODS: Between May 2019 and January 2020, patients with kidney stones undergoing flexible ureteroscopic Ho:YAG laser lithotripsy were enrolled. A K-type thermocouple was applied for intraoperative temperature measurement. Laser was activated at different power (1 J/20 Hz and 0.5 J/20 Hz) and irrigation (0 ml/min, 15 ml/min and 30 ml/min) settings, temperature-time curve was drawn and time needed to reach 43 °C without irrigation was documented. RESULTS: Thirty-two patients were enrolled in our study. The temperature-time curve revealed a quick temperature increase followed by a plateau. With 15 ml/min or 30 ml/min irrigation, 43 °C was not reached after 60 s laser activation at both 1 J/20 Hz and 0.5 J/20 Hz. At the power setting of 1 J/20 Hz and irrigation flow rate of 15 ml/min, the temperature rise was significantly higher than other groups. Without irrigation, the time needed to reach 43 °C at 1 J/20 Hz was significantly shorter than that at 0.5 J/20 Hz (8.84 ± 1.41 s vs. 13.71 ± 1.53 s). CONCLUSION: Ho:YAG laser lithotripsy can induce significant temperature rise in calyceal fluid. With sufficient irrigation, temperatures can be limited so that a toxic thermal dose is not reached, when irrigation is closed, the temperature increased sharply and reached 43 °C in a few seconds.

Robotic-assisted laparoscopic pyeloplasty as management for recurrent ureteropelvic junction obstruction: a comparison study with primary pyeloplasty.

BACKGROUND: To analyze the perioperative parameters and outcomes of robotic-assisted laparoscopic pyeloplasty (RALP) for recurrent ureteropelvic junction obstruction (UPJO) and compare them with our series of RALP for primary UPJO. Secondary pyeloplasty can be a challenging procedure because of ureteral devascularization, fibrosis and dense stricture formation. Robotic approach could be adjunct to these repairs. METHODS: Between August 2015 to March 2019, 96 patients in our hospital underwent RALP, with 32 patients as secondary intervention for recurrent UPJO. We compared the perioperative parameters of RALP for both primary UPJO and recurrent UPJO. Patient demographics, perioperative parameters, postoperative outcomes and complications from both groups were analyzed and compared. RESULTS: RALP was successfully performed for all cases in both groups. The median operating time was longer for secondary RALP than for primary RALP [125 (108.5-155) vs. 151 (120-190) minutes, P=0.004]. There were no conversions to open surgery or significant perioperative complications. No difference in blood loss, transfusion rate and perioperative complication rates was noted between the two groups. The success rates were 98.44% (63/64) and 96.88% (31/32) at a median follow up of 32 and 20 months (P=0.001) for the primary and secondary groups, respectively. CONCLUSIONS: Secondary RALP is associated with significantly longer operative time as compared to primary RALP, especially during the exposure of the UPJO, however it is a safe surgical modality for recurrent UPJO with durable outcome. RALP should be an alternative treatment modality for recurrent UPJO whenever the facility and expert are available.

Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis.

Accumulative reports have documented the critical functions of long non-coding RNAs (lncRNAs) in the progression of malignant tumors, including bladder cancer (BCa). LncRNA ARAP1-AS1 was chosen to be the object of this study due to it was significantly upregulated in the BCa samples of TCGA database. qRT-PCR further validated the dysregulation of ARAP1-AS1 in 88 pairs of BCa tissues and six BCa cells. Kaplan Meier analysis was utilized to analyze the prognostic value of ARAP1-AS1 for patients with BCa. To evaluate the oncogenic property of ARAP1-AS1 in bladder cancer, loss-of-function assays were conducted in two BCa cells in which ARAP1-AS1 was expressed highest. Mechanically, ARAP1-AS1 was enriched in the cytoplasm of BCa cells, suggesting that ARAP1-AS1 might act as a ceRNA to regulate gene expression and biological processes in bladder cancer. It was certified that ARAP1-AS1 can bind with miR-4735-3p in BCa cells. Moreover, functional assays supported the hypothesis that miR-4735-3p is a tumor suppressor in BCa. Additionally, NOTCH2 mRNA could be targeted by miR-4735-3p in BCa cells. The results of all mechanism experiments indicated that ARAP1-AS1 regulated miR-4735-3p/NOTCH2 axis in BCa by acting as a ceRNA. All our research findings may bring novel insights into the treatment of bladder cancer.

Efficacy of ultra-mini percutaneous nephrolithotomy and retrograde intrarenal surgery in the treatment of 2-3 cm lower calyceal stones / Eficacia de la nefrolitotomía percutánea ultramini y la cirugía intrarrenal retrógrada en el tratamiento de cálculos caliceales inferiores de 2-3 cm

Abstract We aimed to compare the efficacy and safety of ultra-mini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) for the management of lower calyceal stones. A group of 136 patients with a single lower calyceal stone (2-3 cm in diameter) was divided into the UMP or RIRS groups. The average operation time in the RIRS group was significantly longer than that in the UMP group, and the intraoperative blood loss in the former was markedly less than that in the latter. Besides, in the RIRS group, the decreased value of postoperative Hb was obviously lower, the postoperative hospital stay was evidently shorter, and the total hospitalization expenses were markedly less than those in UMP group were. Moreover, the success rate of the first-stage lithotripsy in the UMP group was notably higher than that in RIRS group. The RIRS group had an obviously lower VAS score but a markedly higher BCS score than the UMP group six hours after surgery. At 24 h after operation, the levels of serum CRP, TNF-α and IL -6 in patients in both groups were remarkably increased, and they were evidently lower in the RIRS group than those in the UMP group were. Three days after surgery, the levels of serum CRP, TNF-α and IL -6 were notably lower in the UMP group than those in RIRS group were. RIRS and UMP are safe and effective in the treatment of 2-3 cm lower calyceal stones. The first-stage UMP is characterized by a high stone-free rate (SFR), short operation time and low postoperative infection risk, while RIRS is associated with less blood loss and low total expenses.

Resumen Nuestro objetivo fue comparar la eficacia y seguridad de la nefrolitotomía percutánea ultramini (UMP) y la cirugía intrarrenal retrógrada (CRIR) en el manejo quirúrgico de los cálculos caliceales inferiores. Un grupo de 136 pacientes con un solo cálculo calicial inferior (2-3 cm de diámetro) se dividió en un grupo UMP o un grupo CRIR. El tiempo de operación promedio en el grupo CRIR fue significativamente más largo que en el grupo UMP, y la pérdida de sangre intraoperatoria en el primero fue marcadamente menor que en el segundo. Además, en el grupo CRIR, el valor disminuido de la Hb postoperatoria fue obviamente menor, la estancia hospitalaria postoperatoria fue evidentemente más corta y los gastos totales de hospitalización fueron notablemente menores que los del grupo UMP. Además, la tasa de éxito de la litotricia de primera etapa en el grupo UMP fue notablemente más alta que en el grupo CRIR. El grupo CRIR tuvo una puntuación VAS obviamente más baja pero una puntuación BCS marcadamente más alta que el grupo UMP a seos horas después de la operación. A las 24 h después de la operación, los niveles séricos de PCR, TNF-α e IL -6 en los pacientes de ambos grupos aumentaron notablemente y fueron evidentemente más bajos en el grupo CRIR que en el grupo UMP. Tres días después de la operación, los niveles séricos de PCR, TNF-α e IL -6 fueron notablemente más bajos en el grupo UMP que en el grupo CRIR. Los procedimientos CRIR y el UMP son seguros y eficaces en el tratamiento de cálculos caliciales inferiores de 2-3 cm. El UMP de primera etapa se caracteriza por tener una tasa libre de cálculo (SFR) alta, un tiempo de operación corto y un riesgo de infección posoperatorio bajo, y el RIRS se caracteriza por una menor pérdida de sangre y gastos totales bajos.

Identification of new hub genes associated with bladder carcinoma via bioinformatics analysis.

AIMS AND BACKGROUND: Bladder carcinoma (BC) is one of the most common malignant cancers worldwide. Several genes related to the mechanism of BC have been studied in recent years, but the current understanding of BC is still rather limited. This study aimed to find new differentially expressed genes (DEGs) associated with the occurrence and development of BC. METHODS: In this work, we downloaded gene expression data from Gene Expression Omnibus under accession number GSE27448, which included 10 GeneChips from urinary BC tissues and 5 from normal tissues. DEGs were identified by the LIMMA package in R. Then the protein-protein interactions (PPIs) networks were analyzed with the database of Search Tool for the Retrieval of Interacting Genes, and gene ontology (GO) was applied to explore the underlying function of the DEGs using the Database for Annotation, Visualization and Integrated Discovery. RESULTS: A total of 2,068 DEGs were found between BC and normal tissues. These genes were involved in 49 functional clusters. The top 10 highest degree nodes, such as POLR2F/2H (DNA directed RNA polymerase II polypeptide F/polypeptide H) and RPS14/15 (ribosomal protein S14/S15), were proven to be hub nodes in the PPIs network. ITGA7 (integrin, alpha 7), GRB14 (growth factor receptor-bound protein 14), CDC20 (cell division cycle 20) and PSMB1 (proteasome subunit, beta type, 1) were significant DEGs identified in the functional clusters. CONCLUSIONS: Genes such as POLR2F/2H, RPS14/15, ITGA7, GRB14, CDC20 and PSMB1 were forecast to play important roles in the occurrence and progression of BC.

Bioinformatics analysis of the target gene of fibroblast growth factor receptor 3 in bladder cancer and associated molecular mechanisms.

The aim of the present study was to elucidate the molecular mechanisms of fibroblast growth factor receptor 3 (FGFR3) activation via overexpression or mutation of the FGFR3 target gene in bladder cancer (BC). The transcription profile data GSE41035, which included 18 BC samples, containing 3 independent FGFR3 short hairpin (sh)RNA, and 6 control samples, containing enhanced green fluorescent protein (EGFP) shRNA, were obtained from the National Center of Biotechnology Information Gene Expression Omnibus database. The Limma package with multiple testing correction was used to identify differentially expressed genes (DEGs) between FGFR3 knockdown and control samples. Gene ontology (GO) and pathway enrichment analysis were conducted in order to investigate the DEGs at the functional level. In addition, differential co-expression analysis was employed to construct a gene co-expression network. A total of 196 DEGs were acquired, of which 101 were downregulated and 95 were upregulated. In addition, a gene signature was identified linking FGFR3 signaling with de novo sterol biosynthesis and metabolism using GO and pathway enrichment analysis. Furthermore, the present study demonstrated that the genes NME2, CCNB1 and H2AFZ were significantly associated with BC, as determined by the protein-protein interaction network of DEGs and co-expressed genes. In conclusion, the present study revealed the involvement of FGFR3 in the regulation of sterol biosynthesis and metabolism in the maintenance of BC; in addition, the present study provided a novel insight into the molecular mechanisms of FGFR3 in BC. These results may therefore contribute to the theoretical guidance into the detection and therapy of BC.

Notch-1 regulates proliferation and differentiation of human bladder cancer cell lines by inhibiting expression of Krüppel-like factor 4.

Inhibition of Notch signaling pathways, consisting of 4 highly conserved receptors (Notch 1-4), induces expression of Krüppel-like transcription factors (KLFs) linked to bladder cancer tumorigenesis and metastasis. Effects of Notch-1 knockdown on cell proliferation, differentiation and KLF4 levels in bladder cancer cell lines were investigated. PsiRNA1­mediated Notch-1 and KLF4 knockdown models and control model without the psiRNA1 vector were constructed using bladder cancer cell lines T24 and BIU87. Cell proliferation, apoptosis and expression of Notch-1 and KLF4 were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry assay with Annexin V-FITC/PI staining, and reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis, respectively. Proliferation was assessed in Notch-1 and/or KLF4 knockdown. The results showed that Notch-1 mRNA and protein expression levels were significantly lower following psiRNA1 vector transfection in both cell lines (P<0.05). Growth and proliferation of both cell lines were significantly inhibited by Notch-1 knockdown (P<0.05), and more G0/G1 arrest and apoptosis were observed compared to those in the control groups (P<0.05). The effects were time-dependent, peaking between 24-48 h and declining by 72 h. KLF4 expression was significantly higher in the Notch-1 knockdown group than in control cells (P<0.05). Notch-1 knockdown cell proliferation was significantly lower than that of Notch-1 and KLF4 knockdown (P<0.05). In conclusion, Notch-1 may act as an oncogene, regulating the proliferation and differentiation of bladder cancer cells by inhibiting KLF4. Pending further exploration of pathway variations and crosstalk, these pathways may be useful targets for bladder cancer therapy.