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A PTAL-miR-101-FN1 Axis Promotes EMT and Invasion-Metastasis in Serous Ovarian Cancer.
Molecular Therapy: Oncology ( IF 5.3 ) Pub Date : 2019-12-11 , DOI: 10.1016/j.omto.2019.12.002
Haihai Liang 1, 2 , Mengxue Yu 1 , Rui Yang 1 , Lu Zhang 1, 2 , Lijia Zhang 1 , Di Zhu 1 , Hongwei Luo 1 , Yaozhen Hong 1 , Tong Yu 1, 2 , Jian Sun 1, 2 , Hongli Shan 1, 2 , Yunyan Gu 3
Affiliation  

Long non-coding RNAs (lncRNAs) play vital roles in the metastasis and invasion of cancer cells. Systematic analysis of ovarian cancer (OvCa) expression profiles suggests that deregulation of lncRNA AC004988.1, designated promoting transition-associated lncRNA (PTAL), is involved in OvCa progression. However, the underlying mechanism of PTAL in OvCa remains unknown. In this study, we showed that PTAL was significantly upregulated in mesenchymal subtype samples compared with epithelial subtype samples from TCGA serous OvCa datasets. PTAL expression was positively correlated with the expression of fibronectin1 (FN1), whereas PTAL and FN1 were negatively correlated with miR-101 expression in the mesenchymal OvCa samples. In addition, knockdown of PTAL inhibited cell migration and invasion and blunted the progression of metastasis in vitro. Meanwhile, knockdown of PTAL increased the expression of miR-101 and subsequently inhibited the expression of FN1. Importantly, PTAL positively regulated the expression of FN1 through sponging of miR-101 and promoted OvCa cell metastasis by regulating epithelial-mesenchymal transition. Overall, our study demonstrates the role of PTAL as a miRNA sponge in OvCa and suggests that PTAL may be a potential target for preventing OvCa metastasis.



中文翻译:

PTAL-miR-101-FN1轴促进浆液性卵巢癌的EMT和侵袭转移。

长的非编码RNA(lncRNA)在癌细胞的转移和侵袭中起着至关重要的作用。卵巢癌(OvCa)表达特征的系统分析表明,Onc的进展与lncRNA AC004988.1的失调有关,这种表达被称为促进转移相关的lncRNA(PTAL)。但是,OvCa中PTAL的潜在机制仍然未知。在这项研究中,我们显示,与来自TCGA浆液OvCa数据集的上皮亚型样品相比,间充质亚型样品中的PTAL明显上调。在间充质OvCa样品中,PTAL表达与纤连蛋白1(FN1)的表达呈正相关,而PTAL和FN1与miR-101的表达呈负相关。此外,PTAL的抑制可抑制细胞迁移和侵袭,并阻碍转移进程体外。同时,敲低PTAL可增加miR-101的表达,并随后抑制FN1的表达。重要的是,PTAL通过miR-101的海绵化正向调节FN1的表达,并通过调节上皮-间质转化促进OvCa细胞转移。总体而言,我们的研究证明了PTAL作为OvCa中的miRNA海绵的作用,并暗示PTAL可能是预防OvCa转移的潜在靶标。

更新日期:2019-12-11
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