Panigrahi Gati K, Ramteke Anand, Birks Diane, Abouzeid Ali Hamdy E, Venkataraman Sujatha, Agarwal Chapla, Vibhakar Rajeev, Miller Lance D, Agarwal Rajesh, Abd Elmageed Zakaria Y, Deep Gagan
Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, India.
Oncotarget. 2018 Feb 17;9(17):13894-13910. doi: 10.18632/oncotarget.24532. eCollection 2018 Mar 2.
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 (Exo) and normoxic (Exo) conditions. We identified 292 miRNAs loaded in both Exo and Exo. The top 11 miRNAs with significantly higher level in Exo compared to Exo 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 Exo compared to Exo 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 = 0.66, < 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.
缺氧及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。我们曾报道，人PCa细胞在缺氧条件下分泌的外泌体（直径为30 - 150 nm的纳米囊泡）可促进未成熟PCa细胞的侵袭性和干性。在此，我们鉴定了PCa细胞在缺氧条件下分泌的外泌体中所携带的独特微小RNA（miRNA）。使用TaqMan阵列miRNA芯片，我们分析了人PCa LNCaP细胞在缺氧（Exo）和常氧（Exo）条件下分泌的外泌体中的miRNA谱。我们鉴定出Exo和Exo中均携带的292种miRNA。与Exo相比，Exo中水平显著更高的前11种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Exo相比，Exo中表达水平显著更低的前9种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，在从PCa患者血清中分离的外泌体中，两种差异表达的miRNA，即miR - 885（表达增加）和miR - 521（表达降低）表现出相似的表达模式。此外，通过癌症基因组图谱（TCGA）前列腺腺癌（PRAD）基因组数据集分析，miR - 204和miR - 222在前列腺肿瘤中呈现出相关的表达模式（Pearson = 0.66，< 0.0001）。总体而言，本研究鉴定了缺氧PCa细胞分泌的外泌体中差异表达的独特miRNA，并提示它们作为PCa患者缺氧生物标志物的潜在用途。
