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Targeting of KDM5A by miR-421 in Human Ovarian Cancer Suppresses the Progression of Ovarian Cancer Cells

机译:MIR-421在人卵巢癌中靶向KDM5A抑制了卵巢癌细胞的进展

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Purpose: The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes cell growth in many human cancers. A series of functional experiments were conducted to explore the role of miR-421/KDM5A in ovarian cancer cells and their underlying molecular mechanisms. Materials and Methods: Public microarray databases were analyzed to assess KDM5A and miR-421 expression in ovarian cancer. KDM5A was predicted to be a target of miR-421 using software analysis. The expression of the miR-421/KDM5A regulatory axis in ovarian cancer and the mechanisms of its effects on proliferation, migration, and invasion of ovarian cancer cell lines were investigated. Results: Compared with normal ovarian tissues, the expression of KDM5A mRNA and protein was elevated (P 0.05), and miR-421 expression was reduced in ovarian cancer tissue (P 0.05). miR-421 was found to bind specifically to the KDM5A gene. Silencing KDM5A or overexpressing miR-421 significantly inhibited proliferation, migration, and invasion of OVCAR-8 and SKOV-3 cells. Similarly, compared with nude mice injected with cells transfected with empty capsids, the in vivo proliferation rate of OVCAR-8 cells after miR-421 overexpression was reduced significantly. Conclusion: The miR-421/KDM5A regulatory axis plays an important role in the development and progression of ovarian cancer cells.
机译:目的:视网膜母细胞瘤结合蛋白RBP2(KDM5A)是组蛋白脱甲基化酶,其促进许多人类癌症中的细胞生长。进行了一系列功能实验,以探讨miR-421 / kdm5a在卵巢癌细胞及其潜在的分子机制中的作用。材料和方法:分析公共微阵列数据库以评估卵巢癌中的KDM5A和MIR-421表达。预计KDM5A使用软件分析预测为miR-421的目标。研究了MIR-421 / KDM5A调节轴在卵巢癌中的表达及其对卵巢癌细胞系的增殖,迁移和侵袭的影响的机制。结果:与正常卵巢组织相比,KDM5A mRNA和蛋白质的表达升高(P <0.05),卵巢癌组织中的miR-421表达降低(P <0.05)。发现miR-421特异性地结合KDM5A基因。沉默的KDM5A或过表达MIR-421显着抑制OVCAR-8和SKOV-3细胞的增殖,迁移和侵袭。类似地,与注射用空衣壳转染细胞的细胞的裸鼠相比,miR-421过表达后的卵巢-8细胞的体内增殖速率显着降低。结论:MIR-421 / KDM5A监管轴在卵巢癌细胞的开发和进展中起着重要作用。

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