Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany.
Department of Gynecology, University Medical Center Hamburg-Eppendorf, Germany.
Mol Oncol. 2018 Nov;12(11):1935-1948. doi: 10.1002/1878-0261.12371. Epub 2018 Oct 9.
Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in tumor development and progression. The current study focuses on the influence of exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA profiles were determined in exosomes from plasma of 106 EOC patients, eight ovarian cystadenoma patients, and 29 healthy women by TaqMan real-time PCR-based miRNA array cards containing 48 different miRNAs. In cell culture experiments, the impact of miR-200b and miR-320 was determined on proliferation and apoptosis of ovarian cancer cell lines. We report that miR-21 (P = 0.0001), miR-100 (P = 0.034), miR-200b (P = 0.008), and miR-320 (P = 0.034) are significantly enriched, whereas miR-16 (P = 0.009), miR-93 (P = 0.014), miR-126 (P = 0.012), and miR-223 (P = 0.029) are underrepresented in exosomes from plasma of EOC patients as compared to those of healthy women. The levels of exosomal miR-23a (P = 0.009, 0.008) and miR-92a (P = 009, 0.034) were lower in ovarian cystadenoma patients than in EOC patients and healthy women, respectively. The exosomal levels of miR-200b correlated with the tumor marker CA125 (P = 0.002) and patient overall survival (P = 0.019). MiR-200b influenced cell proliferation (P = 0.0001) and apoptosis (P < 0.008). Our findings reveal specific exosomal miRNA patterns in EOC and ovarian cystadenoma patients, which are indicative of a role of these miRNAs in the pathogenesis of EOC.
特定的 microRNAs（miRNAs）被包裹在 exosomes 中，调节肿瘤发生和发展过程。本研究重点关注 exosomes 中的 miRNAs 在卵巢上皮性癌（EOC）发病机制中的影响。通过 TaqMan 实时 PCR 基于 miRNA 阵列卡测定了来自 106 例 EOC 患者、8 例卵巢囊腺瘤患者和 29 例健康女性血浆中的 miRNA 谱，该阵列卡包含 48 种不同的 miRNAs。在细胞培养实验中，测定了 miR-200b 和 miR-320 对卵巢癌细胞系增殖和凋亡的影响。我们报告说，miR-21（P=0.0001）、miR-100（P=0.034）、miR-200b（P=0.008）和 miR-320（P=0.034）明显富集，而 miR-16（P=0.009）、miR-93（P=0.014）、miR-126（P=0.012）和 miR-223（P=0.029）在 EOC 患者血浆中的 exosomes 中含量较低与健康女性相比。与 EOC 患者和健康女性相比，卵巢囊腺瘤患者血浆中的 exosomal miR-23a（P=0.009，0.008）和 miR-92a（P=0.009，0.034）水平较低。miR-200b 的 exosomal 水平与肿瘤标志物 CA125（P=0.002）和患者总生存（P=0.019）相关。miR-200b 影响细胞增殖（P=0.0001）和凋亡（P<0.008）。我们的研究结果揭示了 EOC 和卵巢囊腺瘤患者中特定的 exosomal miRNA 模式，表明这些 miRNA 在 EOC 的发病机制中起作用。
