Development and first-in-human study of PSMA-targeted PET tracers with improved pharmacokinetic properties.

PURPOSE: A series of new 68Ga-labeled tracers based on [68Ga]Ga-PSMA-617 were developed to augment the tumor-to-kidney ratio and reduce the activity accumulation in bladder, ultimately minimize radiation toxicity to the urinary system. METHODS: We introduced quinoline group, phenylalanine and decanoic acid into different tracers to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Their binding affinity onto LNCaP cells was determined through in vitro saturation assays and competition binding assays. In vivo metabolic study, PET imaging and biodistribution experiment were performed in LNCaP tumor-bearing B-NSG male mice. The most promising tracer was selected for first-in-human study. RESULTS: Four radiotracers were synthesized with radiochemical purity (RCP) > 95% and molar activity in a range of 20.0-25.5 GBq/µmol. The binding affinities (Ki) of TWS01, TWS02 to PSMA were in the low nanomolar range (< 10 nM), while TWS03 and TWS04 exhibited binding affinities with Ki > 20 nM (59.42 nM for TWS03 and 37.14 nM for TWS04). All radiotracers exhibited high stability in vivo except [68Ga]Ga-TWS03. Micro PET/CT imaging and biodistribution analysis revealed that [68Ga]Ga-TWS02 enabled clear tumor visualization in PET images at 1.5 h post-injection, with higher tumor-to-kidney ratio (T/K, 0.93) and tumor-to-muscle ratio (T/M, 107.62) compared with [68Ga]Ga-PSMA-617 (T/K: 0.39, T/M: 15.01) and [68Ga]Ga-PSMA-11 (T/K: 0.15, T/M: 24.00). In first-in-human study, [68Ga]Ga-TWS02 effectively detected PCa-associated lesions including primary and metastatic lesions, with lower accumulation in urinary system, suggesting that [68Ga]Ga-TWS02 might be applied in the detection of bladder invasion, with minimized radiation toxicity to the urinary system. CONCLUSION: Introduction of quinoline group, phenylalanine and decanoic acid into different tracers can modulate the binding affinity and pharmacokinetics of PSMA in vivo. [68Ga]Ga-TWS02 showed high binding affinity to PSMA, excellent pharmacokinetic properties and clear imaging of PCa-associated lesions, making it a promising radiotracer for the clinical diagnosis of PCa. Moreover, TWS02 with a chelator DOTA could also label 177Lu and 225Ac, which could be used for PCa treatment without significant side effects. TRIAL REGISTRATION: The clinical evaluation of this study was registered On October 30, 2021 at https://www.chictr.org.cn/ (No: ChiCTR2100052545).

Solitary Fibrous Tumor of the Prostate Shown on FAPI PET/CT.

ABSTRACT: Solitary fibrous tumors are fibroblast tumors that occur mainly in the peritoneum, extremities, and pleura. Here, we report the MRI, FDG PET/CT, and FAPI PET/CT findings of a rare prostate solitary fibrous tumor. A 57-year-old man was pathologically diagnosed with a solitary fibrous tumor. To detect any systemic metastases or other primary lesions, the patient underwent FDG PET/CT and FAPI PET/CT examination sequentially. Mild FDG uptake was observed in the primary prostatic lesion, but there was a significant uptake of FAPI in the prostate. This case highlighted that FAPI PET/CT may outperform FDG PET/CT in identifying solitary fibrous tumors.

Distributed model-free formation control of networked fully-actuated autonomous surface vehicles.

This paper presents a distributed constant bearing guidance and model-free disturbance rejection control method for formation tracking of autonomous surface vehicles subject to fully unknown kinetic model. First, a distributed constant bearing guidance law is designed at the kinematic level to achieve a consensus task. Then, by using an adaptive extended state observer (AESO) to estimate the total uncertainties and unknown input coefficients, a simplified model-free kinetic controller is designed based on a dynamic surface control (DSC) design. It is proven that the closed-loop system is input-to-state stable The stability of the closed-loop system is established. A salient feature of the proposed method is that a cooperative behavior can be achieved without knowing any priori information. An application to formation control of autonomous surface vehicles is given to show the efficacy of the proposed integrated distributed constant bearing guidance and model-free disturbance rejection control.

Deep-Learning-Guided Student Intelligent Classroom Management System.

Aiming at the limitations of old-fashioned instructing knowledge and the insufficiency of existing dynamically managed classrooms, a deep-learning-guided Unity3D-based intelligent classroom management system and the corresponding instrument support were proposed. We first build a virtual scene and import Unity3D motors, in order to improve practical fake action proofs through C# script and prefix system. Subsequently, we attempt to solve the permission arrangement proposition in multiperson entity scenes, and accordingly, we complete the cognitive assistance module using authorization strategy. Our system can provide different students with tailored permissions, foresee text, video, and some flexible functions. Our system can be divided into multiple Spring Cloud frameworks. We further leverage the Redis to optimize the system architecture. The system can be conveniently applied in chemistry instructing with clear virtual auditions under the government direct supervision. It can effectively address authority issues in real scenarios while enhancing the learning efficiency and increasing accessibility. A set of intelligent classroom behavior system based on deep learning that supported by cunning learning methods are proposed accordingly. It can complete the classroom perception ministry. It can optimally conduct status monitoring as well as classroom assignment and discussion services through deep learning vision techniques such as face perception and facial expression analysis. Extensive experimental results have shown the competitive performance of our method.

[Corrigendum] MicroRNA­379­5p plays a tumor­suppressive role in human bladder cancer growth and metastasis by directly targeting MDM2.

Following the publication of the above article, an interested reader drew to the authors' attention that the cell and invasion migration assay data featured in Figs. 2C and 5D contained two pairs of overlapping panels, such that the data appeared to have been derived from the same original sources, even though the data panels were intending to show the results from differently performed experiments. Moreover, there was also an instance of duplicated data panels comparing between the si­NC/cell invasion and si­NC/cell migration assay panels in Fig. 4C. After having examined their original data, the authors have realized that inadvertent errors were made during the process of compiling these figures. Corrected versions of Figs. 2, 4 and 5, incorporating all the data from one of the repeated experiments, are shown opposite and on the next page. The authors all agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also regret any inconvenience caused to the readership of the Journal. [Oncology Reports 57: 3502­3508, 2017; DOI: 10.3892/or.2017.5607].

[Corrigendum] MicroRNA­335 is downregulated in bladder cancer and inhibits cell growth, migration and invasion via targeting ROCK1.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in Fig. 3 on p. 4382, the 'Invasion' assay data for the negative control (NC) experiments for the T24 and EJ cell lines appeared to contain an overlap of data, such that they may have been derived from the same original source even though the data were purportedly intended to show the results from differently peformed experiments. The authors have re­examined their original data, and realize that this figure was inadvertently assembled incorrectly. The revised version of Fig. 3, showing alternative data from one of the repeated experiments, is shown below. Note that this error did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 13: 4379-4385, 2016; DOI: 10.3892/mmr.2016.5055].

Molecular classification of patients with NMIBC predicts the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine-immunohistochemistry-based classification.

OBJECTIVE: To investigate the relationships between non-muscle invasive bladder cancer molecular subtypes and predict the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine. METHODS: A total of 160 patients with T1 stage non-muscle invasive bladder cancer were enrolled in this study. Fifty-three patients underwent anthracycline (Pirarubicin and Pharmorubicin) therapy and 107 patients accepted gemcitabine therapy. Uroplakin II and CK20 were categorized as immunohistochemistry (IHC) markers for luminal subtype, whereas CK5/6 and CD44 were categorized as immunohistochemistry markers for basal subtype. The cluster results with immunohistochemical score indicated that non-muscle invasive bladder cancer can be subgrouped into three major classes. RESULTS: Class 2 showed the luminal-like characteristics, whereas class 3 showed the basal-like characteristics. Class 1 showed no high expression of luminal or basal-associated immunohistochemistry markers. The molecular subtype is an independent risk factor for recurrence-free survival (P = 0.030) and progression-free survival (P = 0.006) in patients with T1 stage non-muscle invasive bladder cancer. In class 1 and class 2 (luminal-like) subtypes, gemcitabine and anthracycline show no difference in recurrence-free survival and progression-free survival. Gemcitabine was associated with reduced recurrence compared with anthracycline (P = 0.039) in class 3 (basal-like) subtypes and show no difference in decreasing progression. CONCLUSIONS: The molecular classification based on immunohistochemical results is an independent risk factor for the prognosis of non-muscle invasive bladder cancer with T1 stage. Different therapeutic methods should be selected according to different molecular subtypes.

CTLA-4 +49A/G Polymorphism Increases the Susceptibility to Bladder Cancer in Chinese Han Participants: A Case-Control Study.

Cytotoxic T cell antigen-4 (CTLA-4) is reportedly involved in the development of bladder cancer (BC). This research was designed to address the potential link between the +49A/G polymorphism in CTLA-4 gene and BC susceptibility. In total, 355 BC cases and 435 match controls from Chinese Han individuals were included eventually. The PCR-RFLR method was utilized to screen for this polymorphism. The +49A/G polymorphism was shown to increase the risk of BC. Subgroup analyses showed that this polymorphism was linked to an increased susceptibility to BC among individuals aged < 60 years, smokers and drinkers. Additionally, this polymorphism significantly correlated with tumor node metastasis and tumor size (≥3 cm). To sum up, this study reveals that the CTLA-4 +49A/G polymorphism could increase the risk of BC in Chinese Han people. Further large cohort studies with enough sample sizes are urgently warranted to verify the findings of this present study.

Hsa_circRNA_100146 Acts as a Sponge of miR-149-5p in Promoting Bladder Cancer Progression via Regulating RNF2.

BACKGROUND: Mounting evidence has demonstrated that circular RNAs (circRNAs) play indispensable roles in the progression of bladder cancer. Public database mining showed that hsa_circRNA_100146 (circRNA_100146) was highly expressed in bladder cancer. This study aimed to characterize the biological role of circRNA_100146 and clarify the underlying mechanism in bladder cancer. METHODS: We evaluated the relationship between circRNA_100146 expression and clinicopathological features. Furthermore, gain- and loss-of-function studies were conducted in bladder cancer cells via transfection with gene-carrying plasmids (over-expression) or specific short hairpin RNAs (knockdown). Moreover, computational algorithms and dual-luciferase reporter assays were performed to explore the possible mechanisms of action. Additionally, in vivo xenograft experiments were performed to further analyze the effect of circRNA_100146 on tumor growth. RESULTS: Our data showed that circRNA_100146 expression was increased in bladder cancer tissues and cell lines, and that high expression of circRNA_100146 was correlated with poor patient prognosis. Upregulation of circRNA_100146 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, whereas knockdown of circRNA_100146 displayed opposite effects on bladder cancer cells. Notably, circRNA_100146 could combine with miR-149-5p and promote ring finger protein 2 (RNF2) expression, thereby facilitating the progression of bladder cancer. Furthermore, overexpression of RNF2 reversed the effects of circRNA_100146 knockdown on the biological behaviors of bladder cancer cells. The in vivo experiments revealed that downregulation of circRNA_100146 dramatically delayed tumor growth. CONCLUSION: Our findings indicate that circRNA_100146 functions as a sponge of miR-149-5p in promoting bladder cancer progression by regulating RNF2 expression and that circRNA_100146 may serve as a novel biomarker in human bladder cancer.

Long non-coding RNA DLX6-AS1 facilitates bladder cancer progression through modulating miR-195-5p/VEGFA signaling pathway.

In this study, we aim at investigating the expression and regulation role of long non-coding RNA (lncRNA) DLX6-AS1 in bladder cancer (BC). DLX6-AS1 was highly expressed in BC tissues and significant negative correlation with the 5-year survival in the BC patients. The results showed that the proliferation, migration and invasion activities of BC cells were promoted by DLX6-AS1 overexpression, while cell apoptosis was repressed. However, knockdown DLX6-AS1 presented an pposite regulatory effect, and DLX6-AS1 knockdown delayed tumor in vivo. The potential target of DLX6-AS1 in BC was predicted and verified by RIP, RNA pull-down, and dual-luciferase reporter assays as miR-195-5p. The results showed that miR-195-5p was down-regulated in BC tissues, the expression of which was significantly negative correlated with DLX6-AS1 expression. In addition, the results also showed that miR-195-5p targeted and down-regulated the VEGFA. Knockdown of DLX6-AS1 up-regulated miR-195-5p expression and down-regulated VEGFA expression. Moreover, down-regulation of VEGFA expression caused by DLX6-AS1 inhibited phosphorylation of Raf-1, MEK1/2, and ERK1/2, while miR-195-5p inhibitors abolished the effect of silencing DLX6-AS1 expression. Our study demonstrated that DLX6-AS1 played an oncogenic role in BC through miR-195-5p-mediated VEGFA/Ras/Raf/MEK/ERK pathway.

SLC14A1 (UT-B) gene rearrangement in urothelial carcinoma of the bladder: a case report.

BACKGROUND: Bladder cancer (BC) is a common and deadly disease. Over the past decade, a number of genetic alterations have been reported in BC. Bladder urothelium expresses abundant urea transporter UT-B encoded by Slc14a1 gene at 18q12.3 locus, which plays an important role in preventing high concentrated urea-caused cell injury. Early genome-wide association studies (GWAS) showed that UT-B gene mutations are genetically linked to the urothelial bladder carcinoma (UBC). In this study, we examined whether Slc14a1 gene has been changed in UBC, which has never been reported. CASE PRESENTATION: A 59-year-old male was admitted to a hospital with the complaint of gross hematuria for 6 days. Ultrasonography revealed a size of 2.8 × 1.7 cm mass lesion located on the rear wall and dome of the bladder. In cystoscopic examination, papillary tumoral lesions 3.0-cm in total diameter were seen on the left wall of the bladder and 2 cm to the left ureteric orifice. Transurethral resection of bladder tumor (TURBT) was performed. Histology showed high-grade non-muscle invasive UBC. Immunostaining was negative for Syn, CK7, CK20, Villin, and positive for HER2, BRCA1, GATA3. Using a fluorescence in situ hybridization (FISH), Slc14a1 gene rearrangement was identified by a pair of break-apart DNA probes. CONCLUSIONS: We for the first time report a patient diagnosed with urothelial carcinoma accompanied with split Slc14a1 gene abnormality, a crucial gene in bladder.

lncRNA MORT Regulates Bladder Cancer Behaviors by Downregulating MicroRNA-146a-5p.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in the progression of various cancers. lncRNA MORT is downregulated in bladder cancer, while its function in this disease is unknown. METHODS: lncRNA MORT and miR-146a-5p expression in 56 bladder cancer patients was detected by RT-qPCR. Correlations between MORT and miR-146a-5p were analyzed by Pearson's correlation coefficient. CCK-8 and flow transwell assays were applied to examine the behavioral changes in HT-1197 and HT-1376. RESULTS: We found that miR-146a-5p was upregulated, while lncRNA MORT was downregulated in bladder cancer. miR-146a-5p and MORT were inversely and significantly correlated in tumor tissues. Overexpression of miR-146a-5p promoted, while overexpression of lncRNA MORT inhibited the invasion, migration, and proliferation of cells of bladder cancer cell lines. In addition, overexpression of lncRNA MORT inhibited miR-146a-5p; miR-146a-5p overexpression failed to significantly affect lncRNA MORT expression but attenuated its inhibitory effects on cancer cell behaviors. CONCLUSION: lncRNA MORT may regulate bladder cancer cell behaviors by downregulating miR-146a-5p.

Investigation of Leptin G19A polymorphism with bladder cancer risk: A case-control study.

BACKGROUND: A host of studies show Leptin (LEP) G19A polymorphism is correlated with the risk of various cancers, but the connection of this polymorphism with bladder cancer (BC) risk has not been reported. MATERIALS AND METHODS: This association was in explored in a case-control study involving 355 BC cases and 435 controls (all Chinese Han). Polymerase chain reaction-restriction fragment length polymorphism was conducted to genotype LEP G19A polymorphism. Analyses of allele and genotype distribution were evaluated using chi-square test. Continuous data were assessed by an independent samples t test or one-way ANOVA test. Odds ratio (OR) and 95% confidence interval (CI) were determined by logistic regression. RESULTS: LEP G19A polymorphism was significantly associated with a lower risk of BC (AA vs GG: adjusted OR, 0.40, 95% CI, 0.20-0.83, P = .013; AA + GA vs GG: adjusted OR, 0.70, 95% CI, 0.52-0.93, P = .015; AA vs GA + GG: adjusted OR, 0.45, 95% CI, 0.22-0.91, P = .026). In addition, A allele was associated with decreased risk for BC (A vs G: OR, 0.70, 95% CI, 0.55-0.89, P = .003). Stratified analyses by females, non-drinkers, and non-smokers all returned considerable relations. Furthermore, LEP G19A polymorphism was correlated with tumor size, tumor node metastasis, and distant metastasis in BC patients. CONCLUSIONS: LEP G19A polymorphism is associated with a less risk of BC.

The association between matrix metalloproteinase-7 genetic variant and bladder cancer risk in a Chinese Han population.

The circulating matrix metalloproteinase-7 (MMP-7) levels are associated with the risk of bladder cancer (BC). MMP-7 gene -181A/G polymorphism may influence the expression of MMP-7 by affecting the transcriptional activity. A case-control study comprising 355 BC patients and 435 age- and gender-matched healthy controls was conducted in a Chinese Han population. The genotype of MMP-7 gene -181A/G polymorphism was determined by using polymerase chain reaction-restriction fragment length polymorphism method. Data revealed that MMP-7 gene -181A/G polymorphism increased the risk of BC under the homozygous and allelic models. However, no association between MMP-7 gene -181A/G polymorphism and BC risk was obtained after adjusting for age, gender, smoking habits and drinking habits. Subgroup analyses showed MMP-7 gene -181A/G polymorphism was associated with increased risk for BC among the smokers and drinkers. Furthermore, AG or GG genotype of -181A/G polymorphism was associated with larger tumor size and lymphatic metastasis in BC patients. To sum up, MMP-7 gene -181A/G polymorphism is not associated with the susceptibility to BC. However, subgroup analyses obtain significant association among the groups of smokers and drinkers. Larger studies in other ethnic groups are needed to ascertain the contribution of MMP-7 gene -181A/G polymorphism to BC risk.

Metabolomic profiling identifies novel biomarkers and mechanisms in human bladder cancer treated with submucosal injection of gemcitabine.

Bladder cancer (BCa) is a common urinary tract malignancy with frequent recurrences after initial resection. Submucosal injection of gemcitabine prior to transurethral resection of bladder tumor (TURBT) may prevent recurrence of urothelial cancer. However, the underlying mechanism remains unknown. In the present study, ultra­performance liquid chromatography Q­Exactive mass spectrometry was used to profile tissue metabolites from 12 BCa patients. The 48 samples included pre­ and post­gemcitabine treatment BCa tissues, as well as adjacent normal tissues. Principal component analysis (PCA) revealed that the metabolic profiles of pre­gemcitabine BCa tissues differed significantly from those of pre­gemcitabine normal tissues. A total of 34 significantly altered metabolites were further analyzed. Pathway analysis using MetaboAnalyst identified three metabolic pathways closely associated with BCa, including glutathione, purine and thiamine metabolism, while glutathione metabolism was also identified by the enrichment analysis using MetaboAnalyst. In search of the possible targets of gemcitabine, metabolite profiles were compared between the pre­gemcitabine normal and post­gemcitabine BCa tissues. Among the 34 metabolites associated with BCa, the levels of bilirubin and retinal recovered in BCa tissues treated with gemcitabine. When comparing normal bladder tissues with and without gemcitabine treatment, among the 34 metabolites associated with BCa, it was observed that histamine change may be associated with the prevention of relapse, whereas thiamine change may be involved in possible side effects. Therefore, by employing a hypothesis­free tissue­based metabolomics study, the present study investigated the metabolic signatures of BCa and found that bilirubin and retinal may be involved in the mechanism underlying the biomolecular action of submucosal injection of gemcitabine in urothelial BCa.

MR urethrography versus X-ray urethrography compared with operative findings for the evaluation of urethral strictures.

PURPOSE: We compared the accuracy of magnetic resonance (MR) urethrography and X-ray urethrography with operative findings for urethral strictures and observed their effects on treatment. MATERIALS AND METHODS: A total of 87 male patients (10-85 years of age) treated from January 2015 to December 2016 were included in the study. X-ray and MR urethrograms were performed for all patients to determine the location, length, and degree of urethral strictures and the organizational structure around the urethra, and the results were compared with the operative findings. One-way analysis of variance (ANOVA) was performed to compare the lengths of the urethral strictures determined by the two methods with the operative findings. A value of P < 0.05, calculated using GraphPad software, indicated statistical significance. RESULTS: Urethral stricture was more clearly shown on MR urethrography than on X-ray urethrography. The stricture length measured by conventional X-ray urethrography [(2.17 ± 0.65) cm] was much longer than that measured by MR urethrography [(1.68 ± 0.67) cm]. The surgical findings [(1.66 ± 0.70) cm] were significantly different from X-ray urethrography findings (F = 24.660, P = 0.000), but no significant difference was observed between the surgical findings and the stricture length measured by MR urethrography (F = 0.040, P = 0.842). CONCLUSION: Urethral strictures can be displayed more clearly and accurately by MR urethrography than by X-ray urethrography. MR urethrography is expected to become a necessary and standard procedure for the preoperative examination of urethral strictures.

ZNF433 positively regulates the beta-catenin/ TCF pathway in prostate cancer and enhances the tumorigenicity of cancer cells.

BACKGROUND: Prostate cancer often shows the over-activation of beta-catenin/t-cell factor (TCF) signaling. It remains largely unknown how the beta-catenin/TCF transcriptional machinery is tightly controlled. METHODS: The ZNF433 mRNA and protein levels in the clinical tissues were examined using q-PCR, Western blot and immunohistochemistry. The phenotypes of prostate cancer cells were examined using MTT assay, Boyden chamber assay and anchorage-independent assay. The interaction between ZNF433 and beta-catenin was evaluated by immunoprecipitation. RESULTS: In the present study, ZNF433 was upregulated in prostate cancer samples, and promoted the growth and migration of prostate cancer cells. Furthermore, ZNF433 was the binding partner of beta-catenin and activated beta-catenin/TCF signaling in prostate cancer. Moreover, ZNF433 enhanced the binding between beta-catenin and TCF4. In addition, NC043, small antagonist for beta-catenin/TCF complex, inhibited the malignant behaviors of prostate cancer cells driven by ZNF433. CONCLUSION: In summary, these studies demonstrate the tumor-promoting roles of ZNF433 in prostate cancer, and suggesting that ZNF433 was a potential target for the treatment.

[Inhibin B level helps evaluate the testicular function of prepubertal patients with varicocele].

OBJECTIVE: To investigate the role of the serum inhibin B (INHB) level in evaluating the testicular function of the prepubertal patient with varicocele (VC) after high ligation of the spermatic vein (HLSV). METHODS: This study included 31 prepubertal male patients with left VC, averaging 12.55 years of age and 9 complicated by right VC. We collected peripheral blood samples before and at 4, 12 and 26 weeks after HLSV as well as spermatic venous blood samples intraoperatively for determination of the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), anti-sperm antibody (AsAb) and serum INHB by ELISA. RESULTS: Compared with the baseline, statistically significant differences were observed in the INHB level in the peripheral blood at 12 and 26 weeks after operation (ï¼»255.18 ± 69.97ï¼½ vs ï¼»141.78 ± 59.82ï¼½ pg/ml, P < 0.05) and that in the spermatic venous blood intraoperatively (ï¼»255.18 ± 69.97ï¼½ vs ï¼»412.44 ± 259.42ï¼½ pg/ml, P < 0.01). Spearman's analysis showed a negative correlation between the level of INHB and that of FSH (r = －0.224, P < 0.01). CONCLUSIONS: The level of serum INHB in the peripheral blood of the prepubertal VC patient is decreased within 6 months after HLSV and negatively correlated with that of FSH. The levels of INHB and FSH may well reflect the testicular function of the prepubertal VC patient.

NOL8, the binding protein for beta-catenin, promoted the growth and migration of prostate cancer cells.

Overactivation of beta-catenin/TCF signaling in prostate cancer is very common. However, how the beta-catenin/TCF complex is regulated in the nucleus remains largely unknown. In this study, we have shown that NOL8, a binding protein of beta-catenin, enhanced the interaction between beta-catenin and TCF4, and activated beta-catenin/TCF signaling. NOL8 is up-regulated in the prostate cancer, and promoted the growth, migration and colony formation of cancer cells. Knocking down the expression of NOL8 inhibited the growth, migration and colony formation of prostate cancer cells. The molecular mechanism study demonstrated that NOL8 promoted the migration and colony formation of cancer cells by activating beta-catenin/TCF signaling. Taken together, this study demonstrated the oncogenic roles of NOL8 in prostate cancer and suggested that NOL8 might be an important therapeutic target for prostate cancer.

Retracted Article: Long noncoding RNA PCA3 regulates glycolysis, viability and apoptosis by mediating the miR-1/CDK4 axis in prostate cancer.

Prostate cancer is one of the common tumor malignancies in men worldwide. Although long noncoding RNAs (lncRNAs) have been demonstrated to play essential roles in the progression of prostate cancer, the roles and potential mechanism of lncRNA prostate cancer antigen 3 (PCA3) remain poorly understood. In the present study, we investigated the role of PCA3 in aerobic glycolysis, viability and apoptosis in prostate cancer cells and probed the interaction between PCA3 and microRNA-1 (miR-1)/cyclin-dependent kinase 4 (CDK4). Here we found that PCA3 and CDK4 were up-regulated while miR-1 was down-regulated in prostate cancer tissues and cells. Moreover, knockdown of PCA3 inhibited aerobic glycolysis and viability and induced apoptosis in prostate cancer cells. Intriguingly, PCA3 was bound to miR-1 and inhibition of miR-1 reversed the regulatory effect of PCA3 knockdown on aerobic glycolysis, viability and apoptosis in prostate cancer cells. Besides, CDK4 was indicated as a target of miR-1 and it was regulated by PCA3 through functioning as a competing endogenous RNA (ceRNA) of miR-1 in prostate cancer cells. The results indicated that PCA3 might drive aerobic glycolysis, viability and apoptosis by regulating the miR-1/CDK4 axis in prostate cancer cells, providing a promising avenue for treatment of prostate cancer.