It is widely accepted that inflammation is an important risk for the development of prostate cancer (PCa). The objective of this study was designed to investigate the potential molecular mechanism of NLR family, pyrin domain-containing protein 3 (NLRP3) inflammasome in the malignant progression of PCa. The expression level of NLRP3 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization. The effects of NLRP3 in the development of PCa by applying gain- and loss-of-function assays in LNCaP and PC3 cell lines were detected by CCK-8, TUNEL, and Transwell migration assays. The underlying mechanism of NLRP3 and caspase-1 in PCa was examined by the rescue experiments, western blotting, and qRT-PCR assays. In addition, the promoting effect of NLRP3 inflammasome was performed with an animal subcutaneous tumorigenesis experiment in vivo. The upregulation of NLRP3 was confirmed in PCa tissues and cell lines. Functionally, using CCK-8, TUNEL, and Transwell migration assays, these results showed that activation of NLRP3/caspase-1 inflammasome by LPS + ATP could enhance the ability of proliferation and migration; and decrease the apoptosis of LNCaP and PC3 cell lines. Western blotting assay showed that the activation of caspase-1 would increase after the stimulation of NLRP3 inflammasome by LPS + ATP. Moreover, the overexpression of NLRP3 promoted, while the knockdown of NLRP3 inhibited the malignant progression in PCa cell lines by positively regulating caspase-1. In addition, the rescue experiments revealed the association among NLRP3 and caspase-1, which showed that the overexpression vectors/inhibitors of caspase-1 could reverse the effect of knockdown/overexpression of NLRP3 in PCa cell lines in vitro. Finally, In in vivo experiment, the suppression of NLRP3 knockdown impaired tumor growth of PCa. Collectively, these results indicated that NLRP3 inflammasome played a vital role in promoting the malignant progression of PCa via the activation of caspase-1. Together, our findings provided insight into the mechanisms of NLRP3/caspase-1 inflammasome and revealed an alternative and potential target for the clinical diagnosis and treatment of PCa.

Di-n-butyl phthalate (DBP) is a kind of ubiquitous chemical linked to hormonal disruptions that affects male reproductive system. However, the mechanism of DBP-induced germ cells toxicity remains unclear. Here, we demonstrate that DBP induces reduction of proliferation, increase of apoptosis and DNA damage dependent on the PTEN/AKT pathway. Mechanistically, DBP decreases PTEN promoter methylation and increases its transcriptional activity, leading to increased PTEN expression. Notably, DNMT3b is confirmed as a target of miR-29b and miR-29b-mediated status of PTEN methylation is involved in the effects of DBP treatment. Meanwhile, DBP decreases AKT pathway expression via increasing PTEN expression. In addition, the fact that DBP decreases the sperm number and the percentage of motile and progressive sperm is associated with downregulated AKT pathway and sperm flagellum-related genes. Collectively, these findings indicate that DBP induces aberrant PTEN demethylation, leading to inhibition of the AKT pathway, which contributes to the reproductive toxicity.

Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR-), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR-, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95 0 /0 CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

Background. Di-N-butylphthalate (DBP) is a kind of unique endocrine toxicity linked to hormonal disruptions that affects the male reproductive system and has given rise to more and more attention. However, the mechanism of DBP-induced testicular injury remains unclear. Here, the objective of this study was to investigate the potential molecular mechanism of miR-506-3p in DBP-induced rat testicular oxidative stress injury via ANXA5 (Annexin A5)/Nrf2/HO-1 signaling pathway. Methods. In vivo, a total of 40 adolescent male rats were treated from 2 weeks with 800mg/kg/day of DBP in 1mL/kg corn oil administered daily by oral gavage. Among them, some rats were also injected subcutaneously with 2nmol agomir-506-3p and/or 10nmol recombinant rat ANXA5. The pathomorphological changes of testicular tissue were assessed by histological examination, and the antioxidant factors were evaluated. Subsequently, ANXA5, Nrf2, and its dependent antioxidant enzymes, such as HO-1, NQO1, and GST, were detected by Western blotting or immunohistochemical staining. In vitro, TM3 cells (Leydig cells) were used to detect the cell activity by CCK-8 and the transfection in the DBP-treated group. Results. Differentially expressed miRNAs between the DBP-treated and normal rats were analyzed, and qRT-PCR showed miR-506-3p was highly expressed in testicular tissues of the DBP-treated rats. DBP-treated rats presented severe inflammatory infiltration, increased abnormal germ cells, and missed cell layers frequently existed in seminiferous tubules, resulted in oxidative stress and decreased testicular function. Meanwhile, upregulation of miR-506-3p aggravated the above changes. In addition, miR-506-3p directly bound to ANXA5, and overexpression of miR-506-3p could reduce the ANXA5 expression and also decrease the protein levels of Nrf2/HO-1 signaling pathway. Additionally, we found that recombinant rat ANXA5 reversed the DBP-treated testicular oxidative stress promoting injury of miR-506-3p in rats. In vivo results were reproduced in in vitro experiments. Conclusions. This study provided evidence that miR-506-3p could aggravate the DBP-treated testicular oxidative stress injury in vivo and in vitro by inhibiting ANXA5 expression and downregulating Nrf2/HO-1 signaling pathway, which might provide novel understanding in DBP-induced testicular injury therapy.

Objective: The aim of this study was to conduct a meta-analysis of 49 relevant studies to evaluate the prognostic value of miRNA-200c in various human malignant neoplasms.

Background: Though previous studies have investigated the efficacy characteristics of several different therapeutic modalities for locally advanced prostate cancer (LAPCa) patients, the available results remained unestablished. Therefore, the aim of this meta-analysis was conducted to clarify such differences. Methods: The online PubMed, EMBASE and Web of Science were comprehensively searched for relevant studies published before September 1st, 2017, and eventually eleven relevant studies met the inclusion criteria. The hazard odds ratios (HRs) with 95% credible interval (CI) were utilized to evaluate the efficacy characteristics of several different therapeutic modalities for LAPCa patients by Markov chain Monte Carlo methods. Results: Five different therapeutic modalities were ultimately enrolled to shed light on the efficacy characteristics for LAPCa patients and seven different clinical outcomes were finally analyzed in this study. The cumulative rank probability of overall survival (OS) or cancer-specific survival (CSS) from best to worst was radiotherapy (RT) + orchiectomy, RT + long-term androgen deprivation therapy (LTADT), RT + short-term androgen deprivation therapy (STADT), LTADT and RT; RT + LTADT, RT + orchiectomy, RT + STADT, LTADT and RT, respectively. Meanwhile, in the terms of progression-free survival (PFS), biochemical failure rate (BFR), disease-free survival (DFS), local progression rate (LPR) and metastasis rate (MR), RT + LTADT as well as RT + STADT had a higher, whereas RT alone or LTADT had a relatively lower treatment effect. Conclusions: All in all, our results indicated that RT + LTADT or RT + orchiectomy was among the best two therapeutic regimens in the prognostic aspects of the patients with LAPCa. Furthermore, in consideration of reducing invasive treatment of eligible patients, RT + LTADT could yield better survival benefit of LAPCa patients, compared with others. In addition, the results of our analysis might provide a reference in the clinical selection. Larger sample sizes of strictly designed randomised controlled trials (RCTs) were wanted to validate our findings.