ABSTRACT
Prostate cancer (PCa) has become the second leading cause of cancer-related mortality in males worldwide. Although the long noncoding RNA DLX6-AS1 has been recognized to be an oncogene in multiple cancers, the biological function and regulatory mechanism of DLX6-AS1 in prostate cancer are still obscure. In the present study, we observed that DLX6-AS1 was significantly upregulated in PCa tissues and cells. Knockdown of DLX6-AS1 inhibited PCa progression by suppressing cell proliferation and accelerating cell apoptosis. Molecular mechanism exploration indicated that DLX6-AS1 acted as a sponge for miR-497-5p and synuclein gamma (SNCG) was a downstream target gene of miR-497-5p. In addition, there was a negative correlation between DLX6-AS1 and miR-497-5p in PCa tissues. Rescue assays showed that SNCG overexpression could partially recover DLX6-AS1 knockdown-mediated inhibition of progression in PCa. Furthermore, xenograft tumor model was established to determine the role of DLX6-AS1 in PCa tumor growth and the results suggested that DLX6-AS1 could facilitate tumor growth by regulating SNCG in vivo. In conclusion, our study investigated the biological function and underlying mechanism of DLX6-AS1 in PCa and validated that DLX6-AS1 functioned as an oncogene through miR-497-5p/SNCG axis.
Subject(s)
Cell Proliferation/genetics , MicroRNAs/metabolism , Prostatic Neoplasms/genetics , Apoptosis , Disease Progression , Gene Expression Regulation, Neoplastic , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Male , Neoplasm Proteins/genetics , RNA, Long Noncoding/genetics , Up-Regulation , gamma-Synuclein/genetics , gamma-Synuclein/metabolismABSTRACT
Prostate cancer (PCa) is known as one of the most common cancers in men all over the world. Previous studies have identified that the pro-inflammatory mediator interleukin-17F (IL-17F) aggravates the progression of several diseases. However, whether IL-17F plays a role in PCa is still lack of enough exploration. In this study, IL-17F expression was strikingly upregulated in PCa tissues. Treatment of IL-17F promoted cell viability at a dose-dependent manner. Further, functional assays were implemented by treatment of 100 ng/ml of IL-17F. Cell viability, proliferation, migration, invasion and stemness were promoted by 100 ng/ml of IL-17F. IL-17F increased the expression of p-PI3K and p-AKT in PCa cells, indicating that IL-17F might activate the PI3K/AKT signalling pathway in PCa cells. LY294002 (the inhibitor of the PI3K/AKT signalling pathway) could reverse the facilitating effects of IL-17F treatment on PCa cell viability, proliferation, migration, invasion and stemness. Taken together, current study revealed that IL-17F facilitated PCa cell malignant phenotypes via activation of the PI3K/AKT signalling pathway, offering a potential therapeutic target for PCa.
