Exosomes are 30-150nM membrane-bound secreted vesicles that are readily isolated from biological fluids such as urine (UEs). Exosomes contain proteins, micro RNA (miRNA), messenger RNA (mRNA), and long non-coding RNA (lncRNA) from their cells of origin. Although miRNA, protein and lncRNA have been isolated from serum as potential biomarkers for benign and malignant disease, it is unknown if lncRNAs in UEs from urothelial bladder cancer (UBC) patients can serve as biomarkers. lncRNAs are > 200 nucleotide long transcripts that do not encode protein and play critical roles in tumor biology. As the number of recognized tumor-associated lncRNAs continues to increase, there is a parallel need to include lncRNAs into biomarker discovery and therapeutic target algorithms. The lncRNA HOX transcript antisense RNA (HOTAIR) has been shown to facilitate tumor initiation and progression and is associated with poor prognosis in several cancers. The importance of HOTAIR in cancer biology has sparked interest in using HOTAIR as a biomarker and potential therapeutic target. Here we show HOTAIR and several tumor-associated lncRNAs are enriched in UEs from UBC patients with high-grade muscle-invasive disease (HGMI pT2-pT4). Knockdown of HOTAIR in UBC cell lines reduces in vitro migration and invasion. Importantly, loss of HOTAIR expression in UBC cell lines alters expression of epithelial-to-mesenchyme transition (EMT) genes including SNAI1, TWIST1, ZEB1, ZO1, MMP1 LAMB3, and LAMC2. Finally, we used RNA-sequencing to identify four additional lncRNAs enriched in UBC patient UEs. These data, suggest that UE-derived lncRNA may potentially serve as biomarkers and therapeutic targets.
This is a case of a proximal corpus cavernosa fracture presenting with scrotal edema and butterfly perineal ecchymosis sparing the penile shaft. Preoperative MRI obviated the need for circumferential incision and degloving of the penis and guided immediate incision over the area of corporal injury. The presentation, diagnostic work-up, and surgical treatment are discussed.
INTRODUCTION AND OBJECTIVES: Androgen signaling is recently suggested to be involved in the growth of bladder cancer. We have previously found that steroid sulfatase (STS) is highly expressed in muscle invasive bladder cancer. STS converts dehydroepiandrosterone sulfate to dehydroepiandrosterone, and is considered one of the key enzymes in androgen signaling pathway. However, the role of STS in bladder cancer has not been elucidated. The purpose of the present study is to determine the clinical and functional significance of STS in bladder cancer.METHODS: STS expression was measured in 170 bladder cancer tissues by immunohistochemistry. Recurrence free survival (RFS) and cancer specific survival (CSS) were evaluated. The functional role of STS on cell proliferation, migration and invasion capacity was evaluated using bladder cancer cell line (TCCSUP and T24) by loss-of-function assay.RESULTS: STS was highly expressed in invasive lesions of bladder cancer tissues. Overexpression of STS was associated with the invasion of bladder cancer evidenced by the findings that incidences of STS positive cancers were 21.3% and 41.2% in non-muscle invasive and muscle invasive bladder cancers, respectively (p ¼ 0.0262). STS positive cancers showed shorter RFS and CSS (p ¼ 0.0083, 0.0014, respectively). In multivariate analysis, STS expression level was identified as an independent prognostic factor for CSS (p ¼ 0.043). Furthermore, in vitro knockdown of STS significantly reduced cell migration and invasion capacities of bladder cancer cells accompanied by up-regulation of E-cadherin and down-regulation of vimentin. Interestingly, the expression of androgen receptor (AR) was not correlated with that of STS, pathological stage or survival of patients with bladder cancer, suggesting that AR is not likely to play an important role in the progression of bladder cancer.CONCLUSIONS: The present study demonstrates that STS is associated with the invasion of bladder cancer and is a useful marker for predicting the progression of bladder cancers. STS might play a role in bladder cancer independent from AR signaling pathway.
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