Department of Urology, Gifu University Graduate School of Medicine, Gifu, Japan.
Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
Cancer Genomics Proteomics. 2021 May-Jun;18(3):253-259. doi: 10.21873/cgp.20256.
To identify novel diagnostic markers for renal cell carcinoma (RCC), we analyzed miRNAs in serum extracellular vesicles (EVs).
EVs were purified from serum of healthy controls and patients with localized and advanced RCC using T-cell immunoglobulin domain and mucin domain-containing protein 4 conjugated to magnetic beads. miRNA profiling of EVs was conducted by microarray analysis. miRNA expression was examined by quantitative reverse transcription-polymerase chain reaction. Lastly, proteomic analysis of RCC cells transfected with a miRNA inhibitor was performed to identify its potential targets.
Microarray analysis revealed that nine miRNAs were increased by more than 1.5-fold in EVs from patients with RCC. Among them, miRNA-4525 was significantly elevated; miRNA-4525 expression was higher in RCC tissue than in the adjacent normal tissue. Proteomic analysis identified alpha fetoprotein and albumin as its potential targets.
These findings suggest the potential of miRNA-4525 in serum EVs as a novel biomarker for advanced RCC.
为了鉴定肾细胞癌（RCC）的新型诊断标志物，我们分析了血清细胞外囊泡（EVs）中的 miRNA。
使用 T 细胞免疫球蛋白结构域和粘蛋白结构域包含蛋白 4 偶联的磁珠从健康对照者和局限性及晚期 RCC 患者的血清中纯化 EVs。通过微阵列分析进行 EVs 的 miRNA 图谱分析。通过定量逆转录聚合酶链反应检查 miRNA 表达。最后，用 miRNA 抑制剂转染 RCC 细胞进行蛋白质组分析，以鉴定其潜在的靶标。
微阵列分析显示，来自 RCC 患者的 EVs 中有 9 种 miRNA 的表达增加了 1.5 倍以上。其中，miRNA-4525 明显升高；RCC 组织中的 miRNA-4525 表达高于相邻的正常组织。蛋白质组分析鉴定甲胎蛋白和白蛋白为其潜在的靶标。
这些发现表明血清 EVs 中的 miRNA-4525 可能成为晚期 RCC 的新型生物标志物。
