LncRNA DLX6-AS1 Promotes Malignant Phenotype and Lymph Node Metastasis in Prostate Cancer by Inducing LARGE Methylation

Long non-coding RNAs (lncRNAs) have recently become recognized as crucial players in cancer cellular events including proliferation, migration, and invasion. Herein, we investigated the potential role of lncRNA DLX6-AS1 in prostate cancer cell malignant behaviors and lymph node metastasis. A differentially expressed lncRNA DLX6-AS1 and its downstream regulatory gene (LARGE) were predicted by analysis in silico. RT-qPCR and western blot analysis results demonstrated that DLX6-AS1 was highly expressed, but LARGE was poorly expressed in prostate cancer tissues and cells. The online website indicated that DLX6-AS1 negatively targeted LARGE expression, which was validated by Pearson correlation analysis and MSP. ChIP, RIP, and RNA pull-down assays further suggested that DLX6-AS1 downregulated LARGE expression through recruitment of DNMT1 to its promoter. We induced DLX6-AS1/LARGE overexpression or knockdown to examine their effects through Edu and Transwell assays, which revealed that DLX6-AS1 overexpression accelerated proliferation, invasion, and migration of prostate cancer cells, and that overexpression of LARGE rescued these effects. Tumors xenografts studies confirmed that DLX6-AS1 promoted lymph node metastasis by regulating LARGE, as evidenced by enhanced expression of MMP-9, uPAR, and cathepsin B. In summary, DLX6-AS1 stimulated prostate cancer malignant progression and lymph node metastasis by inducing DNMT1-mediated LARGE methylation, highlighting a potential therapeutic target against prostate cancer.