Department of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Department of Clinical Laboratory, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China.
Cancer Biomark. 2018;23(4):505-513. doi: 10.3233/CBM-181609.
The aim of this study was to evaluate the correlation of circular RNA itchy E3 ubiquitin protein ligase (Circ-ITCH) expression with clinicopathological features and survival in patients with epithelial ovarian cancer (EOC), and to explore its effect on cells proliferation as well as apoptosis in EOC cells.
Seventy-seven EOC patients underwent surgery were retrospectively reviewed. Tumor tissues and paired adjacent tissues samples were collected, and Circ-ITCH expression was evaluated by quantitative polymerase chain reaction (qPCR). Blank mimic, Circ-ITCH mimic, blank inhibitor and Circ-ITCH inhibitor plasmids were transfected into SKOV3 cells and OVCAR-3 cells, and Counting Kit-8 (CCK-8) was performed to assess cells proliferation and Annexin V (AV)/propidium iodide (PI) was conducted to detect cells apoptosis.
Median value of Circ-ITCH relative expression was 0.697 (0.367-1.106) in tumor tissues, which was lower compared with paired adjacent tissues (1.690 (0.867-2.813)) (P< 0.001), and it negatively correlated with tumor size (P= 0.005) as well as International Federation of Gynecology and Obstetrics (FIGO) stage (P< 0.001) in EOC patients. Multivariate Cox's analysis revealed that high Circ-ITCH expression was an independent predictive factor for favorable OS in EOC patients. Moreover, further in vitro experiments disclosed that Circ-ITCH expression was decreased in several EOC cell lines compared with normal ovarian epithelial cell line, and it inhibited cells proliferation while promoted cells apoptosis in SKOV3 and OVCAR-3 cells.
Circ-ITCH correlates with small tumor size, decreased FIGO stage and prolonged OS, and it inhibits cells proliferation while promotes cells apoptosis in EOC.
本研究旨在评估环状 RNA 瘙痒 E3 泛素蛋白连接酶(Circ-ITCH)表达与上皮性卵巢癌(EOC)患者临床病理特征和生存的相关性,并探讨其对 EOC 细胞增殖和凋亡的影响。
回顾性分析 77 例行手术治疗的 EOC 患者。收集肿瘤组织和配对的相邻组织样本,采用实时定量聚合酶链反应(qPCR)评估 Circ-ITCH 表达。将空白模拟物、Circ-ITCH 模拟物、空白抑制剂和 Circ-ITCH 抑制剂质粒转染至 SKOV3 细胞和 OVCAR-3 细胞,通过细胞计数试剂盒(CCK-8)评估细胞增殖,通过 Annexin V(AV)/碘化丙啶(PI)检测细胞凋亡。
肿瘤组织中 Circ-ITCH 相对表达的中位数为 0.697(0.367-1.106),低于配对的相邻组织(1.690(0.867-2.813))(P<0.001),并且与肿瘤大小(P=0.005)和国际妇产科联盟(FIGO)分期(P<0.001)呈负相关。多因素 Cox 分析显示,Circ-ITCH 高表达是 EOC 患者总生存期(OS)的独立预测因素。此外,进一步的体外实验表明,与正常卵巢上皮细胞系相比,Circ-ITCH 在几种 EOC 细胞系中的表达降低,并且在 SKOV3 和 OVCAR-3 细胞中抑制细胞增殖,同时促进细胞凋亡。
Circ-ITCH 与肿瘤体积小、FIGO 分期降低和 OS 延长相关,可抑制 EOC 细胞增殖,促进细胞凋亡。