Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

RNA-binding motif protein 5 (RBM5) acts as a tumor suppressor in various human cancers and presents with several important characteristics, such as the potentiation of apoptosis, inhibition of the cell cycle, and alternative splicing of Fas and caspase-2 precursor mRNA. However, its role in bladder urothelial carcinoma (BUC) remains unknown. In this study, we found that RBM5 expression was significantly down-regulated in BUC tissues when compared with the adjacent nontumor tissues. The down-regulation of RBM5 activates ß-catenin, which binds to the T-cell factor/lymphocyte enhancer factor element of the miR-432-5p promoter and elevates the expression of miR-432-5p in bladder cancer cells. The up-regulated miR-432-5p directly targets 3'-UTR and depresses RBM5 expression. Thus, RBM5-miR-432-5p-ß-catenin forms a feedback loop in regulating bladder cancer cell apoptosis. Our findings provide evidence that the regulatory feedback loop among RBM5, miR-432-5p, and Wnt-ß-catenin is responsible for the progress of bladder cancer cells.-Zhang, Y.-P., Liu, K.-L., Wang, Y.-X., Yang, Z., Han, Z.-W., Lu, B.-S., Qi, J.-C., Yin, Y.-W., Teng, Z.-H., Chang, X.-L., Li, J.-D., Xin, H., Li, W. Down-regulated RBM5 inhibits bladder cancer cell apoptosis by initiating an miR-432-5p/ß-catenin feedback loop.

[Efficacy of alpha-lipoic acid combined with tamoxifen citrate in the treatment of oligoasthenospermia].

OBJECTIVE: To investigate the effect of alpha-lipoic acid (α-LA) combined with tamoxifen citrate (TC) in the treatment of oligoasthenospermia. METHODS: From June to November 2016, we treated 60 patients with oligoasthenospermia in our Department of Andrology, 30 (the trial group) with oral α-LA (0.6 g, qd) + TC (20 mg, qd) and the other 30 (the control group) with oral L-carnitine (1g, bid) + TC (20 mg, qd). Before and after 3 months of medication, we examined the semen parameters of the patients and the levels of their seminal oxidative stress biomarkers, including methylenedioxyamphetamine (MDA) and total antioxidant capacity (TAC) in the seminal plasma. We also compared the pregnancy rate and adverse reactions between the two groups. RESULTS: Totally, 57 of the patients completed the treatment, 28 in the trial group and 29 in the control. Compared with the baseline, the patients of the trial group showed significant improvement after 3 months of medication in the semen volume (ï¼»2.50 ± 0.71ï¼½ vs ï¼»3.37 ± 0.70ï¼½ ml, P <0.05), sperm concentration (ï¼»12.00 ± 1.65ï¼½ vs ï¼»19.34 ± 2.04ï¼½ ×106/ml, P <0.05), percentage of progressively motile sperm (PMS) (ï¼»18.01 ± 3.01ï¼½% vs ï¼»35.41 ± 6.49ï¼½%, P<0.05), MDA level (ï¼»14.96 ± 2.76ï¼½ vs ï¼»10.04 ± 1.04ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.83 ± 1.02ï¼½ vs ï¼»12.25 ± 1.11ï¼½ U/ml, P <0.05), and so did the controls in the semen volume (ï¼»2.76 ± 0.67ï¼½ vs ï¼»3.36 ± 0.93ï¼½ ml, P <0.05), sperm concentration (ï¼»11.47 ± 1.10ï¼½ vs ï¼»17.77 ± 3.56ï¼½ ×106/ml, P <0.05), percentage of PMS (ï¼»19.22 ± 1.41ï¼½ vs ï¼»36.01 ± 5.22ï¼½ %, P <0.05), MDA level (ï¼»14.66 ± 2.75ï¼½ vs ï¼»10.14 ± 1.01ï¼½ nmol/ml, P <0.05), and TAC in the seminal plasma (ï¼»9.84 ± 0.90ï¼½ vs ï¼»11.14 ± 0.84ï¼½ U/ml, P <0.05). There were no statistically significant differences in the above post-medication parameters between the trial and control groups (P >0.05) except in TAC, which was markedly more improved in the former than in the latter (P <0.05), nor in the percentage of morphologically normal sperm before and after treatment in either of the two groups (P >0.05). After 3 months of treatment, 3 pregnancies were achieved in the trial group and 1 in the control (10.7% vs 3.45%, P >0.05). No obvious adverse events occurred during the treatment. CONCLUSIONS: Alpha-lipoic acid combined with tamoxifen citrate can evidently improve semen parameters in oligoasthenospermia patients by relieving oxidative stress injury.

Neutrophil extracellular traps-associated modification patterns depict the tumor microenvironment, precision immunotherapy, and prognosis of clear cell renal cell carcinoma.

Background: Neutrophil extracellular traps (NETs) are web-like structures formed by neutrophils, and their main function is antimicrobial defense. Moreover, NETs have numerous roles in the pathogenesis and progression of cancers. However, the potential roles of NET-related genes in renal cell carcinoma remain unclear. In this study, we comprehensively investigated the NETs patterns and their relationships with tumor environment (TME), clinicopathological features, prognosis, and prediction of therapeutic benefits in the clear cell renal cell carcinoma (ccRCC) cohort. Methods: We obtained the gene expression profiles, clinical characteristics, and somatic mutations of patients with ccRCC from The Cancer Genome Atlas database (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress datasets, respectively. ConsensusCluster was performed to identify the NET clusters. The tumor environment scores were evaluated by the "ESTIMATE," "CIBERSORT," and ssGSEA methods. The differential analysis was performed by the "limma" R package. The NET-scores were constructed based on the differentially expressed genes (DEGs) among the three cluster patterns using the ssGSEA method. The roles of NET scores in the prediction of immunotherapy were investigated by Immunophenoscores (TCIA database) and validated in two independent cohorts (GSE135222 and IMvigor210). The prediction of targeted drug benefits was implemented using the "pRRophetic" and Gene Set Cancer Analysis (GSCA) datasets. Real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to identify the reliability of the core genes' expression in kidney cancer cells. Results: Three NET-related clusters were identified in the ccRCC cohort. The patients in Cluster A had more metabolism-associated pathways and better overall survival outcomes, whereas the patients in Cluster C had more immune-related pathways, a higher immune score, and a poorer prognosis than those in Cluster B. Based on the DEGs among different subtypes, patients with ccRCC were divided into two gene clusters. These gene clusters demonstrated significantly different immune statuses and clinical features. The NET scores were calculated based on the ten core genes by the Gene Set Variation Analysis (GSVA) package and then divided ccRCC patients into two risk groups. We observed that high NET scores were associated with favorable survival outcomes, which were validated in the E-MTAB-1980 dataset. Moreover, the NET scores were significantly associated with immune cell infiltration, targeted drug response, and immunotherapy benefits. Subsequently, we explored the expression profiles, methylation, mutation, and survival prediction of the 10 core genes in TCGA-KIRC. Though all of them were associated with survival information, only four out of the 10 core genes were differentially expressed genes in tumor samples compared to normal tissues. Finally, RT-PCR showed that MAP7, SLC16A12, and SLC27A2 decreased, while SLC3A1 increased, in cancer cells. Conclusion: NETs play significant roles in the tumor immune microenvironment of ccRCC. Identifying NET clusters and scores could enhance our understanding of the heterogeneity of ccRCC, thus providing novel insights for precise individual treatment.