Background Androgen deprivation therapy (ADT) is the backbone of therapy for advanced prostate cancer (PCa). Despite the good initial response, castration resistance and metastatic progression will inevitably occur. Cancer-associated fibroblasts (CAFs) may be implicated in promoting metastasis of PCa after ADT. Our aim is to investigate the role and mechanism of CAFs-derived exosomes involving in metastasis of PCa after ADT. Methods PCa cells were co-cultured with exosomes derived from 10 nM dihydrotestosterone (DHT)-treated (simulating the high androgen level of prostate cancer microenvironment) or ethanol (ETOH) -treated (simulating the castration level of prostate cancer microenvironment after ADT) CAFs, and their migration and invasion differences under castration condition were examined both in vitro and in vivo. The miRNA profiles of exosomes derived from DHT-treated CAFs and matched ETOH-treated CAFs were analysed via next generation sequencing. The transfer of exosomal miR-146a-5p from CAFs to PCa cells was identified by fluorescent microscopy. The function and direct target gene of exosomal miR-146a-5p in PCa cells were confirmed through Transwell assays, luciferase reporter, and western blot. Results Compared with DHT-treated CAFs, exosomes derived from ETOH-treated CAFs dramatically increased migration and invasion of PCa cells under castration condition. MiR-146a-5p level in exosomes from ETOH-treated CAFs was significantly reduced. The loss of miR-146a-5p may strengthen the epithelial-mesenchymal transition (EMT) to accelerate cancer cells metastasis by modulating epidermal growth factor receptor (EGFR)/ERK pathway. Conclusions CAFs-derived exosomal miR-146a-5p confers metastasis in PCa cells under ADT through the EGFR/ERK pathway and it may present a new treatment for PCa.

BackgroundBladder cancer (BC) is the most common tumor of the urinary system. Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate after surgery, and patients with muscle-invasive bladder cancer (MIBC) have poor quality of life after radical surgery. Understanding the molecular mechanism of bladder cancer is helpful for providing a more appropriate treatment approach. Annexins are calcium-binding proteins and play an important role in different tumor cells. However, the role of the annexin family in bladder cancer has not been studied in detail.MethodsONCOMINE, UALCAN, TIMER2.0, Kaplan-Meier Plotter, cBioPortal, and WebGestalt were utilized in this study.ResultsANXA2, ANXA3, ANXA4, ANXA8, and ANXA9 were significantly increased in bladder tumor tissues, while ANXA6, ANXA7, and ANXA11 were significantly decreased. ANXA1, ANXA2, ANXA3, ANXA5, ANXA6, ANXA7, and ANXA9 had prognostic value in bladder cancer. In addition, specific annexins were specifically expressed in different subtypes of MIBC and were related to the histological morphology of bladder tumors. ANXA1, ANXA2, ANXA3, ANXA5, ANXA6, ANXA7, and ANXA8 were highly expressed in basal-subtype MIBC, while ANXA4, ANXA9, ANXA10, and ANXA11 were mainly expressed in luminal-subtype MIBC. Finally, we analyzed the possible mechanisms of ANXAs in different subtypes of bladder cancer through GO and KEGG analyses and the correlation between ANXAs and immune infiltration in the tumor microenvironment.ConclusionTaken together, our results indicate that annexins might play important roles in BC and have the potential to be used as markers for subtype classification.

As a newly discovered tumor suppressor, the potential function of PAQR3 in human prostate cancer has not been demonstrated. In this study, we report that PAQR3 is able to inhibit the growth and migration of human prostate cancer cells both in vitro and in vivo. Overexpression of PAQR3 inhibits the proliferation of PC3 and DU145 cells by both MTT and colony formation assays. Consistently, knockdown of PAQR3 enhances the proliferation of these cells. In wound-healing and transwell assays, overexpression of PAQR3 reduces the migration of PC3 and DU145 cells, while PAQR3 knockdown increases it. In a tumor xenograft model, overexpression of PAQR3 suppresses tumor growth of PC3 cells in vivo, while PAQR3 knockdown promotes the tumor growth. PAQR3 is also able to inhibit serum-induced phosphorylation of AKT and ERK in both PC3 and DU145 cells. In addition, PAQR3 suppresses the expression of epithelial-mesenchymal transition (EMT) markers in PC3 cells. Collectively, these data indicate that PAQR3 has a tumor suppressive activity in human prostate cancer cells and may stand out as a potential therapeutic target for prostate cancers.