Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Oncology Research Lab, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
Genet Test Mol Biomarkers. 2020 Jul;24(7):399-408. doi: 10.1089/gtmb.2020.0009. Epub 2020 Jun 16.
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.
为了确定Ⅳ型胶原α 6 （COL4A6）表达水平与前列腺癌侵袭和转移之间的关联。我们通过 GEO2R 在线工具分析了三个基因表达综合数据库（GEO），以获得恶性和非恶性前列腺组织之间差异表达基因（DEGs）的集合，并进一步分析了数据库中基因的表达。使用 Western blot 分析、实时定量聚合酶链反应分析和免疫荧光染色来检测基因表达。进行了划痕愈合试验和细胞侵袭 Transwell 试验来测量细胞侵袭，并用 siRNA 敲低基因表达。通过使用生物信息学工具，我们表明该基因是前列腺癌中高度下调的基因之一；此外，前列腺癌中基因启动子的高甲基化与较低的表达水平相关。我们还表明，下调激活前列腺癌细胞中 p-FAK/MMP-9 信号通路的，与从癌症基因组图谱（TCGA）和 GEO 数据库检索到的数据相关，与前列腺癌细胞转移有关。最后，我们发现 COL4A6 蛋白定位于细胞外，其表达与前列腺癌患者的无病生存率呈正相关。我们的结果表明，COL4A6 的下调可能促进前列腺癌的进展和侵袭。此外，和其启动子甲基化状态可能是前列腺癌预后的有价值标志物。
