Shan Weiwei, Li Jun, Bai Yang, Lu Xin
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 128 Shenyang Road in Yangpu District, Shanghai, 200011, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, China.
Tumour Biol. 2016 Apr;37(4):5203-11. doi: 10.1007/s13277-015-4390-2. Epub 2015 Nov 9.
This study aimed to explore the role of miR-339-5p in ovarian cancer. The expression of miR-339-5p in seven ovarian cancer cell lines (Hey, SKOV3, OVCAR5, SKOV3-IP, A2780, CAOV3, and OVCA433) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The miR-339-5p mimic and inhibitor were used to regulate its expression. Migration, invasion, and proliferation were examined. A bioinformatics analysis was used to predict targets, and a dual-luciferase reporter system was applied for validation, along with Western blot verification. Additionally, the association of miR-339-5p and its target genes with ovarian cancer was analyzed based on The Cancer Genome Atlas (TCGA) database. OVCAR5 and SKOV3 had the highest and lowest miR-339-5p expression, respectively. Inhibition of miR-339-5p expression increased the migration and invasion of OVCAR5 cells, while in SKOV3 cells, upregulated miR-339-5p attenuated the migration and invasion ability. Modulation of miR-339-5p had no effect on proliferation. The genes nucleus accumbens associated 1(BEN and BTB (POZ) domain containing) (NACC1) and B cell lymphoma-6 (bcl6) were validated to be targets of miR-339-5p. Clinically, patients with a high expression of NACC1 had a high risk in the survival analysis. miR-339-5p inhibits migration and invasion in ovarian cancer by targeting NACC1 and BCL6. miR-339-5p may be a biomarker of metastasis in ovarian cancer; NACC1 had a predictive value for ovarian cancer progression.
本研究旨在探讨miR-339-5p在卵巢癌中的作用。通过定量实时聚合酶链反应(qRT-PCR)检测了七种卵巢癌细胞系(Hey、SKOV3、OVCAR5、SKOV3-IP、A2780、CAOV3和OVCA433)中miR-339-5p的表达。使用miR-339-5p模拟物和抑制剂来调节其表达。检测了细胞的迁移、侵袭和增殖情况。通过生物信息学分析预测靶点,并应用双荧光素酶报告系统进行验证,同时进行蛋白质印迹验证。此外,基于癌症基因组图谱(TCGA)数据库分析了miR-339-5p及其靶基因与卵巢癌的相关性。OVCAR5和SKOV3细胞中miR-339-5p的表达分别最高和最低。抑制miR-339-5p的表达可增加OVCAR5细胞的迁移和侵袭能力,而在SKOV3细胞中,上调miR-339-5p可减弱其迁移和侵袭能力。调节miR-339-5p对细胞增殖无影响。伏隔核相关1基因(含BEN和BTB(POZ)结构域)(NACC1)和B细胞淋巴瘤-6基因(bcl6)被验证为miR-339-5p的靶点。在临床方面,生存分析显示NACC1高表达的患者具有高风险。miR-339-5p通过靶向NACC1和BCL6抑制卵巢癌的迁移和侵袭。miR-339-5p可能是卵巢癌转移的生物标志物;NACC1对卵巢癌进展具有预测价值。