Gene deletion or gene amplification acts as a driving factor of onset, progress, and metastasis in various cancers, including ovarian cancers. By mining the whole genome data of ovarian cancer patients, we identify the long noncoding RNA PVT1 as the most amplified gene. Knockdown of PVT1 was then achieved using a shRNA in two ovarian cancer cell lines, and cell viability was determined by trypan blue exclusion assay, cell metabolism by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and cell cycle alteration by propidium iodide cell cycle analysis. Potential targeting microRNAs were predicted with starBase v2.0, and direct binding of miR-140 on PVT1 was confirmed by luciferase reporter assay and microRNA pull-down assay. Evolutionary conserved transcription factor-binding site was predicted via rVista 2.0. Our results show that PVT1 was the most amplified gene in ovarian cancer patients, and it was highly correlated with poor survival outcomes. Knockdown of PVT1 caused decreased cell viability, metabolic activity, and smaller proportion of S-phase cells. PVT1 directly bound to miR-140 and acted as a microRNA sponge, while transcription of PVT1 was regulated by the transcription factor FOXO4. In conclusion, viability, metabolism, and cell cycle of ovarian cancers are regulated by the FOXO4/PVT1/miR-140 signaling pathway.

中文翻译：

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lncRNA PVT1的扩增通过与miR-140结合促进卵巢癌增殖。

基因缺失或基因扩增是各种癌症（包括卵巢癌）起病，进展和转移的驱动因素。通过挖掘卵巢癌患者的全基因组数据，我们确定了长的非编码RNA PVT1是扩增最多的基因。然后在两个卵巢癌细胞系中使用shRNA敲低PVT1，并通过台盼蓝排除试验确定细胞活力，通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基- 2-H-溴化四氮唑测定，并通过碘化丙啶细胞周期分析进行细胞周期改变。使用starBase v2.0预测了潜在的靶向microRNA，并通过荧光素酶报告基因测定和microRNA下拉测定证实了miR-140在PVT1上的直接结合。进化保守的转录因子结合位点是通过rVista 2.0预测的。我们的结果表明，PVT1是卵巢癌患者中扩增最多的基因，并且与不良的生存结果高度相关。敲低PVT1导致细胞活力降低，代谢活性降低以及S期细胞比例降低。PVT1直接与miR-140结合并充当microRNA海绵，而PVT1的转录则受转录因子FOXO4调控。总之，卵巢癌的生存力，代谢和细胞周期受FOXO4 / PVT1 / miR-140信号通路的调节。而PVT1的转录受转录因子FOXO4调控。总之，卵巢癌的生存力，代谢和细胞周期受FOXO4 / PVT1 / miR-140信号通路的调节。而PVT1的转录受转录因子FOXO4调控。总之，卵巢癌的生存力，代谢和细胞周期受FOXO4 / PVT1 / miR-140信号通路的调节。