circST6GALNAC6 suppresses bladder cancer metastasis by sponging miR-200a-3p to modulate the STMN1/EMT axis.

Bladder cancer (BCa) is an aggressive malignancy because of its distant metastasis and high recurrence rate. Circular RNAs (circRNAs) exert critical regulatory functions in cancer progression. However, the expression patterns and roles of circRNAs in BCa have not been well investigated. In this study, we first screened circRNA expression profiles using a circRNA microarray of paired BCa and normal tissues, and the expression of circST6GALNAC6 was confirmed by qRT-PCR and fluorescence in situ hybridization (FISH). MTT, colony formation and Transwell assays were performed to measure cell proliferation, migration and invasion. We investigated the regulatory effect of circST6GALNAC6 on miRNA and its target genes to explore the potential regulatory mechanisms of circST6GALNAC6 by chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), MS2-tagged RNA affinity purification (MS2-TRAP), immunofluorescence (IF) and dual luciferase activity assays. A nude mouse xenograft model was used to examine the functions of circST6GALNAC6/STMN1 in tumour metastasis in vivo. We found that 881 circRNAs were significantly dysregulated in BCa tissues compared to normal tissues. circST6GALNAC6(hsa_circ_0088708) was downregulated in BCa tissues and cells. Overexpression of circST6GALNAC6 effectively inhibited the cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and suppressed BCa metastasis in vivo. Mechanistically, we showed that the SP1 transcription factor, which binds to the circST6GALNAC6 mRNA transcript, activates circST6GALNAC6 transcription. Next, we verified that circST6GALNAC6 serves as a sponge that directly binds miR-200a-3p to regulate stathmin (STMN1) expression. Furthermore, we found that STMN1 is involved in circST6GALNAC6/miR-200a-3p axis-regulated BCa EMT and metastasis. Thus, our findings indicate an important underlying mechanism in BCa metastasis by which SP1-induced circST6GALNAC6 sponges miR-200a-3p to promote STMN1/EMT signalling. This mechanism could provide pivotal potential prognostic biomarkers and therapeutic targets for BCa.

The complete mitochondrial genome of the Picasso clownfish: genomic comparisons and phylogenetic inference among Amphiprioninae.

Picasso clownfish belong to the subfamily Amphiprioninae and are considered a variant of the genus Amphiprion. In this study, we first sequenced the complete mitochondrial genome of the Picasso clownfish by Illumina next-generation sequencing technology. The length of the whole mitogenome is 16,727 bp long, with a gene arrangement and composition similar to those of two other Amphiprion species (Amphiprion ocellaris and Amphiprion percula). The topological structure of the phylogenetic tree shows that the Picasso clownfish is more closelyrelated to A. percula than it is to A. ocellaris, suggesting that the Picasso clownfish may be a variant of A. percula.

Role of tumor-associated immune cells in prostate cancer: angel or devil?

Prostate cancer is the most common malignancy in the reproductive system of older males. Androgen deprivation therapy (ADT) is an important treatment for prostate cancer patients. However, almost all prostate cancer patients unavoidably progress to the castration-resistant stage after ADT treatment. Recent studies have shown that tumor-associated immune cells play major roles in the initiation, progression, and metastasis of prostate cancer. Various phenotypes of tumor-associated immune cells have tumor-promoting or antitumor functions mediated by interacting with tumor cells. Here, we review the current knowledge of tumor-associated immune cells in prostate cancer.

The evaluation of monocyte lymphocyte ratio as a preoperative predictor in urothelial malignancies: a pooled analysis based on comparative studies.

In recent years, several studies have reported monocyte lymphocyte ratio (MLR) to predict prognosis in various tumors. Our study was performed to evaluate the association between preoperative MLR between prognostic variables in urothelial carcinoma patients. Systematic literature search was conducted in PubMed, Embase, Web of science. The correlation between preoperative MLR and overall survival (OS), cancer specific survival (CSS), disease free survival (DFS)/relapse free survival (RFS), progression free survival(PFS) was evaluated in urothelial carcinoma patients. Meanwhile, the association between MLR and clinicopathological characteristics was assessed. Finally, 12 comparative studies comprising a total of 6209 patients were included for pooled analysis. The hazard ratios (HRs), odds ratios (ORs)and 95% confidence intervals (CIs) were further analyzed as effect measures. The pooled results demonstrated that elevated preoperative MLR indicated unfavorable OS (HR = 1.29, 95%CI = 1.18-1.39, I2 = 33.6%), DFS/RFS (HR = 1.42, 95%CI = 1.30-1.55, I2 = 0.0%) and CSS (HR = 1.41, 95%CI = 1.29-1.52, I2 = 0.0%). Moreover, the pooled results also suggested that elevated preoperative MLR was correlated with high tumor stage (OR = 1.22, 95%CI = 1.07-1.37, I2 = 0.0%) in urothelial carcinoma patients. No significant association was found between preoperative MLR and PFS in upper urinary tract urothelial carcinoma (UUTUC) patients. Collectively, elevated preoperative MLR predicted poor prognosis in urothelial carcinoma and have the potential to be a feasible and cost-effective prognostic predictor for management of urothelial carcinoma.

What Would a Suprapubic Catheter Indwelling for 4 Years Be Like? A Case Report.

A 35-year-old male of 165 cm height and weight of 65 kg, had a suprapubic catheter indwelling for 4 years without replacement for urethral stricture. The catheter became gradually obstructed, and urine leaked out around the suprapubic catheter. A lumbar abdominal distension, an inferior abdominal mass and renal failure prompted him to seek medical attention in our hospital in September 2018. This clinical case is hereby presented from 3 aspects of imaging, lab examination, and operation.

MicroRNA-200c affects bladder cancer angiogenesis by regulating the Akt2/mTOR/HIF-1 axis.

BACKGROUND: Bladder cancer is one of the most frequent urologic tumours in the world. MicroRNA-200c (miR-200c) has been considered a regulator of tumour angiogenesis. Akt2/mTOR was considered a regulator of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α). However, the mechanism by which miR-200c regulates bladder cancer angiogenesis remains unknown. METHODS: Western blotting and qRT-PCR were used to detect the expression of protein and mRNA, respectively. Cell proliferation, migration and invasion were detected using MTT, wound-healing and transwell assays, respectively. A dual luciferase reporter assay was used to identify the binding site between miR-200c and Akt2. A tube formation assay was also applied to detect the angiogenesis ability. RESULTS: Significantly higher expression levels of HIF-1α and VEGF and lower levels of miR-200c were observed in three types of bladder cancer cell lines. Transfection with the miR-200c mimic markedly inhibited cell viability, angiogenesis, and the expression of VEGF and HIF-1α. Overexpression of miR-200c remarkably suppressed the expression of Akt2, and the binding site between them was identified. Knockdown of Akt2 remarkably decreased the expression of VEGF and HIF-1α by regulating mTOR. miR-200c influenced the expression of VEGF and HIF-1α through the Akt2/mTOR signalling pathway and further regulated angiogenesis in bladder cancer cells. CONCLUSIONS: We proved that miR-200c could suppress HIF-1α/VEGF expression in bladder cancer cells and inhibit angiogenesis, and these regulations were achieved by targeting Akt2/mTOR. This study may provide new insight into the prevention and treatment of bladder cancer.

Curcumin Suppresses microRNA-7641-Mediated Regulation of p16 Expression in Bladder Cancer.

Bladder cancer has a high recurrence rate and requires adjuvant intravesical management after surgery. The use of traditional agents for bladder cancer therapy is constrained by their toxicity and limited efficacy. This emphasizes the need for the development of safer, more effective compounds such as instillation agents. Curcumin is the major component of turmeric, the powdered root of Curcuma longa, which is known for its anti-inflammatory, anti-oxidant and anticancer properties. First, a microarray profiling and qPCR analysis were conducted in the T24 and SV-HUC-1 cell lines. Then, we examined the potential tumorigenicity of miR-7641 in the T24 and SV-HUC-1 cell lines with or without curcumin. Western blot analysis showed that p16 is a target of miR-7641 in T24 cells. We found that, for the first time, curcumin directly downregulates a tumor-promoting microRNA (miRNA), miR-7641, in bladder cancer, which has tumor-promoting characteristics. Curcumin induces the downregulation of miR-7641 and subsequent upregulation of p16 which is a target of miR-7641 at the post-transcriptional level, which leads to the decreased invasion and increased apoptosis of bladder cancer cells. This is the first report to show a direct effect of curcumin on inducing changes in a miRNA suppressor with direct anticancer consequences in bladder cancer. Our study shows that curcumin may be a candidate agent for the clinical management of non-muscle-invasive bladder cancer.

Prognostic roles of tumor associated macrophages in bladder cancer: a system review and meta-analysis.

BACKGROUND: Tumor associated macrophages (TAMs) have multifaceted roles in the development of many tumor types. However, the prognostic value of TAMs in bladder cancer is still not conclusive. EXPERIMENTAL DESIGN: This review evaluated the prognostic value of TAMs density in bladder cancer by reviewing published literatures and integrating the results via a meta-analysis. A systematic search was conducted in PubMed, Embase and Chinese National Knowledge Infrastructure (CNKI), WanFang, and Web of Science databases for relevant studies. Overall survival (OS), relapse free survival (RFS), disease specific survival (DSS), and progression free survival (PFS) were assessed in bladder cancer patients. RESULTS: The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) indicated that TAMs identified with CD68 alone have no significant correlation with OS (HR = 1.01, 95% CI = 1.00-1.02), RFS (HR = 0.99, 95% CI = 0.91-1.06), or PFS (HR = 1.19, 95% CI = 0.70-1.68) in bladder cancer patients. Subgroup analyses involved with Bacillus Calmette Guerin (BCG) treatment or sample locations either showed that CD68+ TAMs presented no prognostic value with regard to OS in bladder cancer patients. However, TAMs detected by CD163 are significantly correlated with poor RFS in bladder cancer patients (HR = 1.54, 95% CI = 1.16-1.92). CONCLUSIONS: Our data indicated that TAMs identified only with CD68 have no significant correlation with the prognosis and clinicopathological parameters of bladder cancer patients. However, TAMs detected with CD163 could serve as a prognostic marker for bladder cancer patients. These findings invite further research on the role of TAM subsets in bladder cancer patients.

An approach to evaluate the reliability of hybridization-based and sequencing-based gene expression profiling technologies.

Hybridization-based and sequencing-based technologies have found a widespread application in gene expression profiling analysis but much ambiguity exists regarding their reliability. This study developed a framework based on three parameters: detection ability, repeatability, and accuracy to evaluate the reliability of gene expression profiling technologies. The fraction of coverage of detected transcript category, the degree of variance for the number of differentially expressed genes (DEGs), the consistency of DEG category, and suspected false discovery rate (sFDR) were first introduced as statistical indices. In order to validate the availability of these indices, based on the same RNA extract, the analysis was performed by comparing gene expression differences between wild-type and transgenic rice using deep sequencing and microarray. The results suggested that the parameters were available and showed advances in the determination of gene expression differences. Based on relative self-comparison design, suspected false positive genes were easily identified from all DEGs detected, which was difficult for quantitative real-time polymerase chain reaction (qRT-PCR) validation when the count of DEGs was enormous. In addition, sFDRs had advantages in the accuracy evaluation for previous datasets.