Taken together, we established a 3D culture model of human prostatic epithelial cells with structural and functional relevance to normal prostate gland and prostate cancer development and also demonstrated that this 3D model might be useful to assess the ability of drugs to restore differentiation as a potential surrogate measure of efficacy for prostate cancer therapy.
Recent advances in immunotherapy are raising hope to treat clear cell renal cell carcinoma (ccRCC) with PD-L1 inhibitors, but only a small portion of patients are PD-L1 positive. The heterogeneous expression pattern of PD-L1 in patient population suggests that PD-L1 expression is under the control of diverse regulatory mechanisms. Although recent studies have identified numerous novel PD-L1 regulators, reports on microRNAs which modulate PD-L1 expression are much scarce. In this study, we confirmed that PD-L1 expression was up-regulated in ccRCC compared to paired normal tissues. Using miRDB and miRTarBase, 11 microRNAs were predicted to target PD-L1. After measuring the microRNA panel with TaqMan assays, we found that microRNA-497-5p down-regulation was associated with PD-L1 up-regulation. In TCGA-KIRC dataset, microRNA-497-5p down-regulation was also associated with PD-L1 up-regulation as well as shorter survival. We further validated that PD-L1 was a direct target of microRNA-497-5p in two RCC cell lines. In addition, microRNA-497-5p inhibited cell proliferation, clone formation and migration, while promoted apoptosis in in-vitro assays. Our study reveals a novel regulatory mechanism of PD-L1 expression and the potential of miR-497-5p as therapeutic target and biomarker deserves further investigation.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.