No abstract

Tumor‐associated macrophages (TAMs) are vital constituents in mediating cell‐to‐cell communication within the tumor microenvironment. However, the molecular mechanisms underlying the interplay between TAMs and tumor cells that guide cell fate are largely undetermined. Extracellular vesicles, also known as exosomes, which are derived from TAMs, are the components exerting regulatory effects. Thus, understanding the underlying mechanism of “onco‐vesicles” is of crucial importance for prostate cancer (PCa) therapy. In this study, we analyzed micro RNA sequences in exosomes released by THP‐1 and M2 macrophages and found a significant increase in miR‐95 levels in TAM‐derived exosomes, demonstrating the direct uptake of miR‐95 by recipient PCa cells. In vitro and in vivo loss‐of‐function assays suggested that miR‐95 could function as a tumor promoter by directly binding to its downstream target gene, JunB, to promote PCa cell proliferation, invasion, and epithelial–mesenchymal transition. The clinical data analyses further revealed that higher miR‐95 expression results in worse clinicopathological features. Collectively, our results demonstrated that TAM‐mediated PCa progression is partially attributed to the aberrant expression of miR‐95 in TAM‐derived exosomes, and the miR‐95/JunB axis provides the groundwork for research on TAMs to further develop more‐personalized therapeutic approaches for patients with PCa.

Prostate cancer is still considered a significant health care challenge worldwide due in part to the distinct transformation of androgen‐dependent prostate cancer (ADPC) into treatment‐refractory castration‐resistant prostate cancer (CRPC). Consequently, there is an urgent need to explore novel molecular mechanisms underlying treatment resistance in ADPC. Although numerous studies have alluded to the role of miR‐200a in several cancers, the biological significance of miR‐200a in prostate cancer remains unknown. After performing microarray analysis and reanalysis of the publicly available Memorial Sloan Kettering Cancer Center dataset, miR‐200a expression was found higher in ADPC tissues and its expression was positively associated with survival of CRPC patients. In vitro studies showed that miR‐200a overexpression in CRPC cells markedly suppressed cellular proliferation and facilitated apoptosis. In vivo studies indicated that overexpression of miR‐200a inhibited growth and metastasis of prostate cancer. The luciferase reporter assay demonstrated that BRD4 is a direct target gene of miR‐200a and it could reverse miR‐200a‐mediated biological effects in prostate cancer cells. Most importantly, our findings indicated that miR‐200a suppresses the progression of CRPC by inhibiting the activation of BRD4‐mediated AR signaling. This finding provides the foundation for the development of more personalized therapeutic approaches for CRPC patients.

No abstract

Prostate cancer (PCa) is the second most common malignant tumors for male patients worldwide. However, whether a history of pre-existing cancer cases may affect the survival of prostate cancer patients is still not fully understood.We identified patients diagnosed with PCa between 2000 and 2014 from the Surveillance, Epidemiology, and End Results (SEER) linked database. We further made propensity score matching and then compared all-cause and cancer-specific survival between patients with and those without a pre-existing cancer. Cox proportional hazards models and Kaplan–Meier analysis were used for survival comparison.A total of 153,255 patients with PCa were included for analysis, of whom 5939 had a history of pre-existing cancer, including hematologic and lymph (11%), intestine (19%), urinary system (36%), head and neck (9%), lung (5%), skin (12%), and others (8%). Patients with a pre-existing cancer had a worse prognosis compared with those without a pre-existing cancer [all-cause death: hazard ratio (HR) = 2.74, P < .001; cancer-special death: HR = 3.98, P < .001]. Importantly, cancers in urinary bladder prior to PCa had a most adverse impact on all-cause (HR = 5.00, P < .001) and cancer-specific death risk (HR = 10.45, P < .001). Time between the pre-existing cancer and PCa had a dose-dependent effect on survival of PCa patients, with a decreased death risk as the increase of the interval time.Pre-existing cancer has a negative impact on the prognosis of patients with PCa, which is most evident in the presence of a pre-existing urinary bladder cancer. Our results provide epidemiologic evidence with low between-group bias, large sample size, and long-term follow-up, highlighting the need for site-, and interval-time-based clinical management for patients with PCa who had a pre-existing cancer.