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环状 RNA 相互作用与肿瘤体积小、FIGO 分期降低和总生存期延长相关,它在卵巢上皮性癌中抑制细胞增殖,同时促进细胞凋亡。

Circ-ITCH correlates with small tumor size, decreased FIGO stage and prolonged overall survival, and it inhibits cells proliferation while promotes cells apoptosis in epithelial ovarian cancer.

机构信息

Department of Orthopedics, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.

Department of Clinical Laboratory, Zaozhuang Municipal Hospital, Zaozhuang, Shandong, China.

出版信息

Cancer Biomark. 2018;23(4):505-513. doi: 10.3233/CBM-181609.

Abstract

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

Circ-ITCH correlates with small tumor size, decreased FIGO stage and prolonged OS, and it inhibits cells proliferation while promotes cells apoptosis in EOC.

摘要

目的

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。

方法

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。

结果

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。

结论

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。

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