Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression. The ERβ-modulated HOTAIR is able to function via antagonizing several microRNAs, including miR-138, miR-200c, miR-204, or miR-217 to impact various oncogenes, including ADAM9, CCND2, EZH2, VEGFA, VIM, ZEB1, and ZEB2, to promote RCC proliferation and invasion. Together, the identification of the ERβ-HOTAIR axis may provide us new biomarkers and/or therapeutic targets to better suppress RCC progression in the future.

ABSTRACT

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BackgroundThe present study sought to identify a panel of DNA markers for noninvasive diagnosis using cell‐free DNA (cfDNA) from urine supernatant or cellular DNA from urine sediments of hematuria patients. A panel of 48 bladder cancer‐specific genes was selected. A next‐generation sequencing‐based assay with a cfDNA barcode‐enabled single‐molecule test was employed. Mutation profiles of blood, urine, and tumor sample from 16 bladder cancer patients were compared. Next, urinary cellular DNA and cfDNA were prospectively collected from 125 patients (92 bladder cancer cases and 33 controls) and analyzed using the 48‐gene panel. The individual gene markers and combinations of markers were validated according to the pathology results. The mean areas under the receiver operating characteristic (ROC) curves (AUCs) obtained with the various modeling approaches were calculated and compared. ResultsThis pilot study of 16 bladder cancer patients demonstrated that gene mutations in urine supernatant and sediments had better concordance with cancer tissue as compared with plasma. Logistic analyses suggested two powerful combinations of genes for genetic diagnostic modeling: five genes for urine supernatant (TERT, FGFR3, TP53, PIK3CA, and KRAS) and seven genes for urine sediments (TERT, FGFR3, TP53, HRAS, PIK3CA, KRAS, and ERBB2). The accuracy of the five‐gene panel and the seven‐gene panel in the validation cohort yielded AUCs of 0.94 [95% confidence interval (CI) 0.91–0.97] and 0.91 (95% CI 0.86–0.96), respectively. With the addition of age and gender, the diagnostic power of the urine supernatant five‐gene model and the urine sediment seven‐gene model improved as the revised AUCs were 0.9656 (95% CI 0.9368–0.9944) and 0.9587 (95% CI 0.9291–0.9883). ConclusionscfDNA from urine bears great diagnostic potential. A five‐gene panel for urine supernatant and a seven‐gene panel for urine sediments are promising options for identifying bladder cancer in hematuria patients.

The androgen receptor (AR) has been linked to bladder cancer (BCa) progression, but if this involves circular RNAs (circRNAs) remains unclear. Here, we find that AR alters the levels of circRNA‐FNTA (circFNTA) to increase BCa cell invasion and chemo‐resistance. Mechanistically, AR represses the RNA editing gene ADAR2 via direct binding to its 5′ promoter region to increase circFNTA levels, which then sponges the microRNA miR‐370‐3p to increase the expression of its host gene FNTA. This AR‐mediated ADAR2/circFNTA/miR‐370‐3p/FNTA pathway then activates KRAS signaling to alter BCa cell invasion and chemo‐sensitivity to cisplatin. A clinical BCa sample survey shows that circFNTA expression is elevated in BCa tissues, and results from a BCa mouse model indicate that depletion of circFNTA leads to the suppression of BCa metastases and increased cisplatin chemo‐sensitivity. Together, based on our results using multiple BCa cell lines and an in vivo mouse model we suggest that targeting this newly identified AR/ADAR2/circFNTA/miR‐370‐3p/FNTA/KRAS axis may lead to the development of therapies to suppress BCa metastasis and to increase its chemo‐sensitivity.

Early studies demonstrated that male melanoma patients have worse survival than female patients, yet the detailed mechanisms for this gender difference remain unclear. We analyzed around 100 cases of human melanoma and found that androgen receptor (AR) positive melanoma patients have worse survival outcomes compared with AR-negative melanoma patients. Here we report that AR can have positive roles to increase melanoma cell invasion in multiple cell lines in vitro and a mouse model in vivo. Mechanism dissection suggest that AR increases melanoma cell invasion via modulating the MITF-AXL signals via altering the miRNA-539-3p/USP13 signaling to increase MITF protein degradation through a reduction of de-ubiquitination. Restoring MITF can reverse AR-enhanced melanoma cell invasion. Together, our results demonstrate that AR can promote melanoma metastasis via altering the miRNA-539-3p/USP13/MITF/AXL signal and targeting this newly identified signal with AR degradation enhancer ASC-J9 may help us to better suppress the melanoma metastasis.

BackgroundSocial media has revolutionized the way people communicate, and it has been widely incorporated into medical practice. However, limited data are available regarding the use of social media by Chinese urologists in their practice.MethodsFrom 2014 to 2016, during the China Urological Association’s (CUA) Annual National Minimally Invasive Urology Academic Conference, an anonymous survey on social media usage was distributed to participant urologists.ResultsThe results of the survey, which was completed by 665 participants, indicate a conspicuous increase in social media use during the last three years. Regression analysis showed that year (2014 compared to 2016 and 2015), institute location (in the eastern region of China) and age (<35 y) were independent predictors of social media use. Rather than for personal use, an increasing number of respondents said they used social media for professional purposes, and for most respondents, social media has had a positive impact on their practice. However, when posting information on social media, few respondents were aware of the issue of protecting patients’ privacy.ConclusionsOur study demonstrates a dramatic increase in social media use among Chinese urologists, which provides great opportunities for online academic communication and medical education. However, unprofessional use of social media in the medical practice may bring about potential risks and challenges for the further development of social media in medical practice.

Compelling evidence suggests that benign prostatic hyperplasia (BPH) development involves accumulation of mesenchymal-like cells derived from the prostatic epithelium by epithelial-mesenchymal transition (EMT). Transforming growth factor (TGF)-β induces EMT phenotypes with low E-cadherin and high vimentin expression in prostatic epithelial cells. Here we report that LPS/TLR4 signalling induces down-regulation of the bone morphogenic protein and activin membrane-bound inhibitor (BAMBI), which enhances TGF-β signalling in the EMT process during prostatic hyperplasia. Additionally, we found that the mean TLR4 staining score was significantly higher in BPH tissues with inflammation compared with BPH tissues without inflammation (5.13 ± 1.21 and 2.96 ± 0.73, respectively; P < 0.001). Moreover, patients with inflammatory infiltrate were more likely to have a higher age (P = 0.020), BMI (P = 0.026), prostate volume (P = 0.024), total IPSS score (P = 0.009) and IPSS-S (P < 0.001). Pearson’s correlation coefficient and multiple regression analyses demonstrated that TLR4 mRNA expression level was significantly positively associated with age, BMI, serum PSA levels, urgency and nocturia subscores of IPSS in the inflammatory group. These findings provide new insights into the TLR4-amplified EMT process and the association between TLR4 levels and storage LUTS, suggesting chronic inflammation as vital to the pathogenesis of BPH.