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综合分析揭示长链非编码 RNA LINC00511 在人卵巢癌中的致癌功能。

An integrated analysis reveals the oncogenic function of lncRNA LINC00511 in human ovarian cancer.

机构信息

Department of Obstetrics and Gynecology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, P.R China.

Department of Gynecology, Yantaishan Hospital, Yantai, Shandong, P.R China.

出版信息

Cancer Med. 2019 Jun;8(6):3026-3035. doi: 10.1002/cam4.2171. Epub 2019 Apr 23.

Abstract

Ovarian cancer is one of the most common female reproductive system malignancies worldwide. Recently, the aberrant long noncoding RNAs (lncRNAs) expression has been identified in multiple cancers. Emerging evidence has highlighted the critical roles of lncRNAs in carcinogenesis and tumor progression, including ovarian cancer. The objective of this study is to comprehensively analyze lncRNAs expression pattern, and explore their clinical significance and underlying mechanism in human ovarian cancer. In this study, we found hundreds of dysregulated lncRNAs in ovarian cancer by performing genome-wide analysis using RNA sequencing data from Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) project, and three microarray datasets from Gene Expression Omnibus (GEO). Moreover, our results revealed that up- or down-regulation of some lncRNAs expression in ovarian cancer is accompanied by their genomic loci copy number amplification or deletion. Importantly, some lncRNAs expression levels are significantly associated with ovarian cancer patients' poor prognosis. Further experimental validation and mechanistic investigation indicate that LINC00511 exerts oncogenic function in ovarian cancer cells through interacting with EZH2 and repressing P21 expression. Taken together, the findings in the current study may provide a useful resource of novel ovarian cancer associated lncRNAs and potential diagnostic biomarker and therapeutic targets for ovarian cancer.

摘要

卵巢癌是全球最常见的女性生殖系统恶性肿瘤之一。最近,在多种癌症中发现了异常的长链非编码 RNA(lncRNA)表达。新出现的证据强调了 lncRNA 在癌症发生和肿瘤进展中的关键作用,包括卵巢癌。本研究的目的是全面分析 lncRNA 的表达模式,并探讨其在人类卵巢癌中的临床意义和潜在机制。在这项研究中,我们通过使用来自 Genotype-Tissue Expression (GTEx) 和 The Cancer Genome Atlas (TCGA) 项目的 RNA 测序数据以及来自 Gene Expression Omnibus (GEO) 的三个微阵列数据集进行全基因组分析,发现了数百个在卵巢癌中失调的 lncRNA。此外,我们的结果表明,在卵巢癌中一些 lncRNA 的表达上调或下调伴随着其基因组位点拷贝数的扩增或缺失。重要的是,一些 lncRNA 的表达水平与卵巢癌患者的不良预后显著相关。进一步的实验验证和机制研究表明,LINC00511 通过与 EZH2 相互作用并抑制 P21 的表达,在卵巢癌细胞中发挥致癌作用。总之,本研究中的发现可能为卵巢癌相关 lncRNA 提供了有用的资源,以及潜在的诊断生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b18c/6558455/ff4612b453c4/CAM4-8-3026-g001.jpg

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