Department of Bioscience and Laboratory Medicine, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564, Japan.
Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8203, Japan.
Molecules. 2022 Jun 20;27(12):3953. doi: 10.3390/molecules27123953.
Ovarian cancer is the most common cause of gynecological malignancy-related mortality since early-stage disease is difficult to diagnose. Advanced clear cell carcinoma of the ovary (CCCO) has dismal prognosis, and its incidence has been increasing in Japan, emphasizing the need for highly sensitive diagnostic and prognostic CCCO biomarkers. Exosomal microRNAs (miRNAs) secreted by tumor cells are known to play a role in carcinogenesis; however, their involvement in ovarian cancer is unclear. In this study, we performed expression profiling of miRNAs from exosomes released by five cell lines representing different histological types of ovarian cancer. Exosomes isolated from culture media of cancer and normal cells were compared for miRNA composition using human miRNA microarray. We detected 143 exosomal miRNAs, whose expression was ≥1.5-fold higher in ovarian cancer cells than in the control. Among them, 28 miRNAs were upregulated in cells of all histological ovarian cancer types compared to control, and three were upregulated in CCCO cells compared to other types. Functional analyses indicated that miR-21 overexpressed in CCCO cells targeted tumor suppressor genes , , , and . The identified miRNAs could represent novel candidate biomarkers to diagnose or monitor progression of ovarian cancer, particularly CCCO.
卵巢癌是妇科恶性肿瘤相关死亡的最常见原因，因为早期疾病难以诊断。晚期透明细胞卵巢癌（CCCO）的预后较差，在日本其发病率一直在增加，这强调了需要高度敏感的诊断和预后 CCCO 生物标志物。肿瘤细胞分泌的细胞外体 microRNAs（miRNAs）已知在致癌作用中发挥作用；然而，其在卵巢癌中的作用尚不清楚。在这项研究中，我们对代表不同组织学类型卵巢癌的五种细胞系释放的 miRNA 进行了表达谱分析。使用人类 miRNA 微阵列比较了来自癌症和正常细胞培养物的培养基中分离的外泌体的 miRNA 组成。我们检测到 143 种外泌体 miRNA，其在卵巢癌细胞中的表达水平比对照细胞高 1.5 倍以上。其中，与对照相比，所有组织学类型的卵巢癌细胞中 28 种 miRNA 上调，而 CCCO 细胞中 3 种 miRNA 上调。功能分析表明，CCCO 细胞中过表达的 miR-21 靶向肿瘤抑制基因 、 、 和 。鉴定的 miRNA 可能代表用于诊断或监测卵巢癌，特别是 CCCO 进展的新型候选生物标志物。
