Downregulation of Collagen Is Associated with Prostate Cancer Progression and Metastasis.

To determine the association between collagen type IV alpha 6 () expression levels and prostate cancer invasion and metastasis. We analyzed three Gene Expression Omnibus (GEO) datasets through the GEO2R online tool to obtain the set of differentially expressed genes (DEGs) between malignant and nonmalignant prostate tissues, and further analyzed the gene's expression in databases. Western blot assays, real-time quantitative polymerase chain reaction analysis, and immunofluorescence staining were used to detect gene expression. Wound healing assays and cell invasion transwell assays were performed to measure cell invasion and siRNA was used to knock down gene expression. Through the use of bioinformatic tools we showed that the gene is one of the highly downregulated genes in prostate cancer; additionally, hypermethylation of the promoter in prostate cancer is correlated with lower expression levels. We also showed that downregulation of , which activates the p-FAK/MMP-9 signaling pathway in prostate cancer cells, is associated with prostate cancer cell metastasis based on data retrieved from The Cancer Genome Atlas (TCGA) and GEO databases. Finally, we found that the COL4A6 protein is localized extracellularly and its expression is positively correlated with disease-free survival of prostate cancer patients. Our results indicate that downregulation of COL4A6 may promote prostate cancer progression and invasion. Additionally, and its promoter methylation status could be valuable markers for prostate cancer prognoses.