Liu Shankun, Liu Ying, Lu Qiang, Zhou Xiao, Chen Li, Liang Weifeng
Department of Gynecology, Tai'an City Center Hospital, Tai'an, Shandong, People's Republic of China.
Department of Obstetrics and Gynecology, The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao, Shandong, People's Republic of China.
Onco Targets Ther. 2018 Oct 12;11:6845-6851. doi: 10.2147/OTT.S167900. eCollection 2018.
Epithelial ovarian cancer (EOC) is among the most common malignant tumors of the endocrine system. Numerous studies have shown that genetic factors are important in the development of EOC, and there is evidence that long noncoding RNA molecules (lncRNAs) can regulate gene expression at the transcription, posttranscription, and epigenetic levels to influence cancer proliferation and invasion, cell differentiation, and apoptosis. However, the roles of lncRNAs in the pathogenesis of EOC remain unclear. Here, we investigated the role of the lncRNA, taurine upregulated gene 1 (), in EOC.
mRNA levels were evaluated in EOC and matched normal tissue samples and in EOC cell lines by quantitative real-time PCR. Lentiviral vectors expressing the lncRNA, , and siRNA targeting were constructed and transfected into EOC cells. MTT and Transwell assays were used to determine the effects of on cell proliferation, migration, and invasion. Western blotting was performed to determine the influence of up- or downregulation on WNT/β-catenin signaling, which is involved in the occurrence and development of cancer.
expression was clearly elevated in EOC compared with control tissue and cells. Moreover, expression was associated with lymphatic metastasis, T stage, and clinical stage in patients with EOC. Downregulation of in EOC inhibited cell proliferation, migration, and invasion. In EOC cells, levels of the WNT/β-catenin pathway factors, β-catenin, cyclin D1, and c-Myc, were significantly up- and downregulated in response to over- and underexpression, respectively.
Our data suggest that knockdown of may represent a novel therapeutic approach for the management of EOC.
上皮性卵巢癌(EOC)是内分泌系统最常见的恶性肿瘤之一。大量研究表明,遗传因素在EOC的发生发展中起重要作用,并且有证据表明长链非编码RNA分子(lncRNAs)可在转录、转录后和表观遗传水平调节基因表达,从而影响癌症的增殖和侵袭、细胞分化及凋亡。然而,lncRNAs在EOC发病机制中的作用仍不清楚。在此,我们研究了lncRNA牛磺酸上调基因1()在EOC中的作用。
通过定量实时PCR评估EOC及其配对的正常组织样本以及EOC细胞系中的mRNA水平。构建了表达lncRNA 以及靶向 的小干扰RNA(siRNA)的慢病毒载体,并将其转染到EOC细胞中。采用MTT和Transwell实验来确定 对细胞增殖、迁移和侵袭的影响。进行蛋白质免疫印迹法以确定 的上调或下调对参与癌症发生发展的WNT/β-连环蛋白信号传导的影响。
与对照组织和细胞相比,EOC中 的表达明显升高。此外, 的表达与EOC患者的淋巴转移、T分期和临床分期相关。EOC中 的下调抑制了细胞增殖、迁移和侵袭。在EOC细胞中,WNT/β-连环蛋白通路因子β-连环蛋白、细胞周期蛋白D1和c-Myc的水平分别随着 的过表达和低表达而显著上调和下调。
我们的数据表明,敲低 可能是一种治疗EOC的新方法。