Role of miR-490-3p in blocking bladder cancer growth through targeting the RNA-binding protein PCBP2.

MiR-490-3p is regarded as a tumor suppressor in many cancers, but whether miR-490-3p is involved in the development of bladder cancer remains unknown. BALB/c nude mice (male, 15-20 g) were used to investigate the role of MiR-490-3p in bladder cancer. The relationship between miR-490-3p and PCBP2 involved in bladder cancer regulation were determined. Cell viability, proliferation, and cell cycle were estimated by cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine (BrdU) detection, and flow cytometry analysis, respectively. In animal experiments, lentivirus was transfected into bladder cancer cells to overexpress miR-490-3p, which were then injected into mice and the change of tumor volume was assessed. Principal findings: The expression of MiR-490-3p was decreased in bladder cancer cells. Overexpression of miR-490-3p inhibited bladder cancer cell viability and proliferation. Moreover, overexpression of miR-490-3p caused cell cycle arrest in bladder cancer cells. The inhibitory effect of miR-490-3p on bladder cancer cells growth could be counteracted by enhancing PCBP2 expression. In vivo, bladder cancer growth in mice was blocked by miR-490-3p upregulation. MiR-490-3p suppressed bladder cancer growth and bladder cancer cell proliferation by down-regulating PCBP2 expression.

Identification of circulating miRNAs as novel prognostic biomarkers for bladder cancer.

MicroRNAs (miRNAs) are a type of ncRNAs with 18-25 nucleotides in length and reported to play crucial roles in human cancers. Bladder cancer is one of the most common causes of cancer-related death. The discovery of new early biomarkers for BC may improve the patients' response to the treatment thus obtaining higher outcomes. The present study identified 7 miRNAs were up-regulated in bladder serum cancer samples compared to normal samples, including hsa-miR-185-5p, hsa-miR-663a, hsa-miR-30c-5p, hsa-miR-3648, hsa-miR-1270, hsa-miR-200c-3p, and hsa-miR-29c-5p. The dysregulation of these miRNAs were correlated to advanced stage and overall survival time in bladder cancer patients. Moreover, we identified a predictive model to predict the prognosis of bladder cancer. Kaplan-Meier survival curve analyses showed that bladder cancer patients with high-risk scores had significantly worse overall survival time than bladder patients with lower risk scores. Furthermore, we constructed a miRNA-mRNA regulating network. Bioinformatics analysis showed these miRNAs were involved in regulating sarcomere organization, positive regulation of multicellular organism growth, phosphorylation, phosphatidylinositol-mediated signaling, and peroxisome proliferator activated receptor signaling pathway. We thought this study could provide novel noninvasive early biomarkers for bladder cancer.

Tea Consumption is Associated with Increased Risk of Kidney Stones in Northern Chinese: A Cross-sectional Study.

Kidney stones are a common urinary system condition that can progress to kidney disease. Previous studies on the association between tea consumption and kidney stones are inconsistent. A cross-sectional study to investigate the association between tea consumption and kidney stones was conducted from 2013 to 2014 and recruited 9,078 northern Chinese adults. A total of 8,807 participants were included in the final analysis. Participants' prevalence of kidney stones was 1.07%, 1.73%, and 2.25% based on their tea consumption frequency of never, occasionally, and often groups, respectively. Compared with the 'never' group, the odds ratios (95% confidence intervals) for the occurrence of kidney stones were 1.57 (1.00-2.46) and 1.65 (1.06-2.57) in the 'occasionally' and 'often' groups, respectively. After adjusting for sex, age, and other potential confounding factors, tea consumption still significantly increased the risk of kidney stones. Tea consumption is independently associated with an increased risk of kidney stones in the investigated population, suggesting that a decrease in the consumption of tea may be a preventive strategy for kidney stones.

Effects of oral finasteride on erectile function in a rat model.

INTRODUCTION: Many clinical studies reported finasteride-related erectile dysfunction, but to date, few animal experiments have focused on it. AIM: To investigate the effects of oral finasteride on erectile function in a rat model. MAIN OUTCOME MEASURES: Erectile responses and morphological changes. METHODS: Adult, male Sprague-Dawley rats were divided into four groups (25/group): (i) control; (ii) castration; (iii) castration with testosterone (T) replacement; and (iv) oral finasteride treatment. Four weeks later, erectile function was measured by the ratio of intracavernosal pressure and mean arterial blood pressure upon electrical stimulation of the cavernous nerve. Serum T and dihydrotestosterone (DHT) and intraprostatic DHT were measured. The weights and histopathological features of the penile corpus cavernosum and prostate were examined. RESULTS: Serum T and DHT and intraprostatic DHT concentrations, erectile function, and mean weights of the corpus cavernosum and prostate were lowest in group 2. There was no significant difference in the serum T concentration and erectile function between groups 4 and 1. However, the serum and intraprostatic DHT concentrations were significantly lower in group 4 than in group 1 (both P < 0.001). The tissue weights of the corpus cavernosum and prostate were reduced by 25.9% and 92.3% in group 4 compared with group 1 (both P < 0.001). Histopathology revealed a significant atrophy of the prostate in groups 2 and 4. There was a significant decrease in the smooth muscle content in group 2, but not in groups 3 and 4. CONCLUSIONS: In a rat model, finasteride treatment for 4 weeks reduces the weight of the corpus cavernosum but appears not to affect the erectile responses to electrical stimulation of the cavernous nerve. As erection is a complex process involving important signaling in the brain, further studies are necessary to demonstrate the long-term effects of finasteride on both central and peripheral neural pathways of erection.

miR-21 as an independent biochemical recurrence predictor and potential therapeutic target for prostate cancer.

PURPOSE: Abnormal miRNA expression is associated with prostate cancer progression. However, the relationship between miRNA and biochemical recurrence after radical prostatectomy is not well established. Thus, we evaluated the miRNA miR-21 as a biomarker to predict the risk of biochemical failure, and as a potential drug target for prostate cancer therapy. MATERIALS AND METHODS: miR-21 levels were assayed using locked nucleic acid in situ hybridization coupled with tissue microarray techniques in 169 radical prostatectomy tissue samples. The Cox proportional hazard model was used to analyze miR-21 expression as an independent predictor of biochemical recurrence. The association of miR-21 with recurrence was estimated using the Kaplan-Meier method. miR-21 was also evaluated as a potential drug target for prostate cancer therapy. RESULTS: miR-21 expression in prostate cancer tissue samples was significantly associated with pathological stage, lymph node metastasis, capsular invasion, organ confined disease, Gleason score, biochemical recurrence and patient followup. Multivariate analysis also indicated that miR-21 expression could be an independent predictor of biochemical recurrence. The 5-year recurrence-free probability for patients positive vs negative for miR-21 expression was 33.9% vs 44.5%. In vivo treatment with antagomir-21 also repressed the tumor growth of DU145 cells in nude mice. CONCLUSIONS: Positive miR-21 expression was associated with poor biochemical recurrence-free survival and predicted the risk of biochemical recurrence in patients with prostate cancer after radical prostatectomy. Accordingly gene therapy using miR-21 inhibition strategies may prove useful for prostate cancer therapy.

Vasoactive intestinal polypeptide, an erectile neurotransmitter, improves erectile function more significantly in castrated rats than in normal rats.

OBJECTIVE: • To investigate the regulatory role of androgen in VIP-mediated erectile effect. Androgen is essential for physiological erection. Vasoactive intestinal polypeptide (VIP) is an important erectile neurotransmitter. While previous studies demonstrated that VIP expression in the penis was androgen-independent, it remains controversial whether androgen has any effect on VIP-mediated erection. MATERIALS AND METHODS: • Male SD rats were divided into a control group, a castration group, and a castration-with-testosterone-replacement group. Four weeks later, each group was subdivided into low and high-dose VIP subgroups and subjected to intracavernous injection of 0.5 and 2 µg VIP, respectively. • Erectile function was tested by recording intracavernosal pressure (ICP) and mean arterial blood pressure (MAP) before and after VIP injection. • The expressions of the VIP-receptor (VPAC2), G-protein stimulatory and inhibitory alpha subunits (Gs-α, Gi-α), and PDE3A in rat corpus cavernosum (CC) was qualified by real-time PCR and Western blot analysis. RESULTS: • Castration reduced erectile function while testosterone restored it. VIP improved erectile function in a dose-dependent manner. • High-dose VIP significantly enhanced erectile function in castrated rats and there was no difference of ICP/MAP among three groups after injection of high-dose VIP. • Low-dose VIP also resulted in a higher improvement of erectile function in castrated rats, although the ICP/MAP was lower in these rats than in the other two groups. VPAC2 and Gs-α were up-regulated while Gi-α and PDE3A were down-regulated in CC of castrated rats. CONCLUSION: • VIP improves erectile function much more significantly in hypogonadal condition, mainly due to the higher expression of VPAC2, Gs-α, and lower expression of Gi-α and PDE3A in CC of castrated rats. Androgen may negatively regulate the erectile effect of VIP.