<p>MicroRNA-939 Directly Targets <em>HDGF</em> to Inhibit the Aggressiveness of Prostate Cancer via Deactivation of the WNT/β-Catenin Pathway</p>

Abstract

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.

Identification of Urinary Exosomal miRNAs for the Non-Invasive Diagnosis of Prostate Cancer

“…PCa has a wide diffusion and represents the second major cause of death worldwide because of its aggressive behaviour. 25 MiRNAs have been suggested to be novel diagnostic/therapeutic instruments, as they could play a role as a biomarker in the diagnosis and may also represent possible targets for new therapies. 26,27 In the case of PCa, the interest in miRNA is linked to the fact that prostate-specific antigen shows several limitations, 28,29 as infection, very common in frail patients.…”

LINC01207 promotes prostate cancer progression by sponging miR‑1182 to upregulate AKT3

“…Accumulating evidence has shown that lncRNA is involved in tumorigenesis and cancer progression ( 33 , 34 ). Abnormal miRNA expression is another factor contributing to tumorigenesis by dysregulating target genes related to PC progression ( 14 , 15 ). Meanwhile, several studies have revealed that lncRNA promotes PC growth mainly by regulating genes and pathways supporting cell proliferation ( 1 , 3 – 5 ).…”

“…Abnormal miRNA expression has also been observed in PC, and complex miRNA regulatory networks and modules have been proposed to regulate PC progression ( 12 , 13 ). Aberrant miRNA expression frequently dysregulates the target genes implicated in carcinogenesis of PC ( 14 , 15 ). Among them, miR-1182 was identified as a tumor suppressor and implicated in the tumorigenesis of different tumor types, such as bladder ( 16 ), ovarian ( 17 ), gastric ( 18 ) and PC ( 19 ).…”

The Wnt Signalling Pathway: A Tailored Target in Cancer

“…Prostate cancer (PCa) is among the most common tumour in male. A recent study by Situ et al [ 72 ] provided evidence for the involvement of the microRNA-939 (miR-939) in PCa. Downregulation of miR-939 was found in tumour tissues at advanced tumour stage, in distant lesions, as well as being associated with poor prognosis.…”