Exosomal microRNA profiling to identify hypoxia-related biomarkers in prostate cancer.
Exosomal microRNA profiling to identify hypoxia-related biomarkers in prostate cancer.
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DOI：
10.18632/oncotarget.24532
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发表时间：
2018-03-02
期刊：
影响因子：
--
通讯作者：
Deep G
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文献类型：
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作者：
Panigrahi GK;Ramteke A;Birks D;Abouzeid Ali HE;Venkataraman S;Agarwal C;Vibhakar R;Miller LD;Agarwal R;Abd Elmageed ZY;Deep G
缺氧和缺氧相关生物标志物的表达与前列腺癌（PCa）的疾病进展和治疗失败相关。我们报道了人类 PCa 细胞在缺氧条件下分泌的外泌体（直径 30-150 nm 的纳米囊泡）可促进初始 PCa 细胞的侵袭性和干性。在这里，我们鉴定了缺氧条件下 PCa 细胞分泌的外泌体中加载的独特 microRNA (miRNA)。使用 TaqMan® 阵列 microRNA 卡，我们分析了人 PCa LNCaP 细胞在缺氧 (ExoHypoxic) 和常氧 (ExoNormoxic) 条件下分泌的外泌体中的 miRNA 图谱。我们鉴定了 ExoHypoxic 和 ExoNormoxic 中加载的 292 个 miRNA。与 ExoNormoxic 相比，ExoHypoxic 中水平显着较高的前 11 个 miRNA 为 miR-517a、miR-204、miR-885、miR-143、miR-335、miR-127、miR-542、miR-433、miR-451、miR-92a 和 miR-181a；与 ExoNormoxic 相比，ExoHypoxic 中表达量显着降低的前 9 个 miRNA 为 miR-521、miR-27a、miR-324、miR-579、miR-502、miR-222、miR-135b、miR-146a 和 miR-491。重要的是，与健康个体相比，从 PCa 患者血清中分离的外泌体中，两种差异表达的 miRNA miR-885（表达增加）和 miR-521（表达减少）显示出相似的表达模式。此外，根据癌症基因组图谱 (TCGA) 前列腺腺癌 (PRAD) 基因组数据集分析，miR-204 和 miR-222 在前列腺肿瘤中显示出相关的表达模式 (Pearson R = 0.66，p < 0.0001)。总体而言，本研究鉴定了缺氧 PCa 细胞分泌的外泌体中具有差异表达的独特 miRNA，并表明它们作为 PCa 患者缺氧生物标志物的潜在用途。
Hypoxia and expression of hypoxia-related biomarkers are associated with disease progression and treatment failure in prostate cancer (PCa). We have reported that exosomes (nanovesicles of 30-150 nm in diameter) secreted by human PCa cells under hypoxia promote invasiveness and stemness in naïve PCa cells. Here, we identified the unique microRNAs (miRNAs) loaded in exosomes secreted by PCa cells under hypoxia. Using TaqMan® array microRNA cards, we analyzed the miRNA profile in exosomes secreted by human PCa LNCaP cells under hypoxic (ExoHypoxic) and normoxic (ExoNormoxic) conditions. We identified 292 miRNAs loaded in both ExoHypoxic and ExoNormoxic. The top 11 miRNAs with significantly higher level in ExoHypoxic compared to ExoNormoxic were miR-517a, miR-204, miR-885, miR-143, miR-335, miR-127, miR-542, miR-433, miR-451, miR-92a and miR-181a; and top nine miRNA with significantly lower expression level in ExoHypoxic compared to ExoNormoxic were miR-521, miR-27a, miR-324, miR-579, miR-502, miR-222, miR-135b, miR-146a and miR-491. Importantly, the two differentially expressed miRNAs miR-885 (increased expression) and miR-521 (decreased expression) showed similar expression pattern in exosomes isolated from the serum of PCa patients compared to healthy individuals. Additionally, miR-204 and miR-222 displayed correlated expression patterns in prostate tumors (Pearson R = 0.66, p < 0.0001) by The Cancer Genome Atlas (TCGA) prostate adenocarcinoma (PRAD) genomic dataset analysis. Overall, the present study identified unique miRNAs with differential expression in exosomes secreted from hypoxic PCa cells and suggests their potential usefulness as a biomarker of hypoxia in PCa patients.