Department of Obstetrics and Gynecology, Central Hospital of Minhang District, Shanghai, China.
Department of Obstetrics and Gynecology, Central Hospital of Minhang District, Shanghai, China -
Minerva Med. 2022 Aug;113(4):707-717. doi: 10.23736/S0026-4806.20.06654-9. Epub 2020 Jun 5.
The purpose of this study was to explore the mechanism by which microRNA-196b exerts a tumor promotion effect on ovarian cancer (OCa).
Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of microRNA-196b in 60 pairs of tumor samples and paracancerous ones collected from patients with ovarian cancer, meanwhile, microRNA-196b expression in human ovarian cancer cell lines and normal ovarian epithelial cell lines were also analyzed by qRT-PCR. Bioinformatics methods suggested that ZMYND11 was predicted the target gene of microRNA-196b and its binding relationship was verified by dual luciferase reporter gene experiment. Then cell counting kit (CCK-8) and 5-Ethynyl-2'-deoxyuridine (EdU) assay were performed to analyze the influence of microRNA-196b overexpression on OCa cell proliferation.
QRT-PCR results showed that microRNA-196b level in OCa tissues was remarkably higher than that in normal ovarian tissues, which was closely relevant to the poor prognosis of tumors. The dual luciferase reporter gene experiments confirmed that microRNA-196b could directly bind to the 3'-UTR of ZMYND11. Overexpression of microRNA-196b remarkably enhanced the proliferation, invasiveness and migratory ability of OCa cells. Meanwhile, overexpression of microRNA-196b significantly decreased ZMYND11 mRNA and protein expression. In addition, ZMYND11 level was also significantly increased in ovarian cancer cells. Compared with the miRNA-NC group, microRNA-196b-mimics + ZMYND11-OE treatment reversed the effect of microRNA-196b-mimics on OCa cell functions.
MicroRNA-196b was highly expressed in OCa tissues, which can promote the proliferation, invasiveness and migratory ability of OCa cells by targeting ZMYND11. In addition, the expression disorder of microRNA-196b was associated with the malignant development of OCa.
本研究旨在探讨 microRNA-196b 对卵巢癌(OCa)发挥肿瘤促进作用的机制。
通过定量实时聚合酶链反应(qRT-PCR)检测 60 对卵巢癌患者肿瘤组织和癌旁组织中 microRNA-196b 的表达,同时分析人卵巢癌细胞系和正常卵巢上皮细胞系中 microRNA-196b 的表达。生物信息学方法提示 ZMYND11 是 microRNA-196b 的靶基因,并通过双荧光素酶报告基因实验验证其结合关系。然后通过细胞计数试剂盒(CCK-8)和 5-乙炔基-2'-脱氧尿苷(EdU)检测分析 microRNA-196b 过表达对 OCa 细胞增殖的影响。
qRT-PCR 结果显示,OCa 组织中 microRNA-196b 水平明显高于正常卵巢组织,与肿瘤的不良预后密切相关。双荧光素酶报告基因实验证实,microRNA-196b 可直接结合 ZMYND11 的 3'-UTR。microRNA-196b 的过表达显著增强了 OCa 细胞的增殖、侵袭和迁移能力。同时,microRNA-196b 的过表达显著降低了 ZMYND11 mRNA 和蛋白表达。此外,卵巢癌细胞中 ZMYND11 水平也明显升高。与 miRNA-NC 组相比,microRNA-196b 模拟物+ZMYND11-OE 处理逆转了 microRNA-196b 模拟物对 OCa 细胞功能的影响。
microRNA-196b 在 OCa 组织中高表达,通过靶向 ZMYND11 促进 OCa 细胞的增殖、侵袭和迁移能力。此外,microRNA-196b 的表达紊乱与 OCa 的恶性发展有关。