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Purpose: MicroRNA-939 (miR-939) has crucial roles in several types of human cancer. However, the expression profile and precise functions of miR-939 in prostate cancer (PCa) are still unclear. This study aimed to determine miR-939 expression in PCa and explore its roles in PCa tumorigenesis. Methods: miR-939 expression was determined in PCa tissues and cell lines using reverse transcription–quantitative polymerase chain reaction. Cell Counting Kit-8, colony formation, and flow cytometric assays were used to determine the role of miR-939 in PCa cell proliferation and apoptosis in vitro, whereas a tumor xenograft model was generated to evaluate the effect of miR-939 on tumor growth in vivo. Transwell assays were performed to investigate whether miR-939 affects the migration and invasiveness of PCa cells. Results: miR-939 was found to be downregulated in PCa tissues and cell lines, and this downregulation was significantly correlated with tumor stage and lymphatic metastasis. Patients with PCa exhibiting low miR-939 expression had shorter overall survival than those exhibiting high miR-939 expression. Exogenous miR-939 expression suppressed PCa cell proliferation, colony formation, migration, and invasion in vitro; enhanced apoptosis in vitro; and decreased tumor growth in vivo. Investigation of the underlying molecular mechanisms revealed hepatoma-derived growth factor (HDGF) as a direct target gene of miR-939 in PCa. HDGF was found to be significantly upregulated in PCa tissues, and its expression was inversely correlated with miR-939 expression. HDGF silencing and miR-939 upregulation showed similar effects in PCa. Restored HDGF expression counteracted the tumor-suppressive activity of miR-939 overexpression in PCa cells. Furthermore, ectopic miR-939 expression inhibited the WNT/β-catenin pathway activation in PCa both in vitro and in vivo by downregulating HDGF. Conclusion: miR-939 functions as a tumor suppressor during PCa tumorigenesis by directly targeting HDGF and deactivating the WNT/β-catenin pathway, suggesting the miR-939/HDGF/WNT/β-catenin pathway as an effective target for PCa therapy. [ABSTRACT FROM AUTHOR]

Coronary collateral circulation (CCC) functions as a natural bypass in the event of coronary obstruction, which markedly improves prognosis in patients with coronary artery disease (CAD). MicroRNAs (miRNAs) have been implicated in multiple physiological and pathological processes, including angiogenesis involved in CCC growth. The roles that miRNA-939 (miR-939) plays in angiogenesis remain largely unknown. We conducted this study to explore the expression of miR-939 in CAD patients and its role in angiogenesis. For the first time, our results indicated that the expression of circulating miR-939 was down-regulated in patients with sufficient CCC compared with patients with poor CCC. Overexpression of miR-939 in primary human umbilical vein endothelial cells (HUVECs) significantly inhibited the proliferation, adhesion and tube formation, but promoted the migration of cells. In contrast, miR-939 knockdown exerted reverse effects. We further identified that γ-catenin was a novel target of miR-939 by translational repression, which could rescue the effects of miR-939 in HUVECs. In summary, this study revealed that the expression of circulating miR-939 was down-regulated in CAD patients with sufficient CCC. MiR-939 abolished vascular integrity and repressed angiogenesis through directly targeting γ-catenin. It provided a potential biomarker and a therapeutic target for CAD. [ABSTRACT FROM AUTHOR]

CD2-associated protein (CD2AP) serves as a slit diaphragm (SD) protein and plays essential roles in maintaining podocyte integrity and reducing proteinuria. MicroRNAs (miRNAs) are novel regulators of gene expression. Podocyte-specific loss of miRNAs would lead to significant proteinuria. Here, we report new evidence in which miRNAs may function to suppress CD2AP expression through a transcriptional way. By scanning human CD2AP promoterin silicofor sequences complementary to known miRNAs, we chose miR-939, miR-148b*, miR-191*, miR-638 as four candidates and transfected them into HEK-293T cells. Dual-luciferase reporter assay identified that only miR-939 significantly reduced the relative luciferase activity of CD2AP promoter region. Further analysis confirmed that the mRNA and protein expressions of CD2AP were also down-regulated by miR-939. In conclusion, we have identified that miR-939 targets CD2AP promoter sequences and suppresses its gene expression. These findings suggest that miRNAs may mediate podocyte injury via reducing the expression of the SD proteins, such as CD2AP. [ABSTRACT FROM AUTHOR]