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鉴定 6 个潜在的长非编码 RNA 作为参与透明细胞肾细胞癌竞争性内源性 RNA 的生物标志物。

Identification of Six Potentially Long Noncoding RNAs as Biomarkers Involved Competitive Endogenous RNA in Clear Cell Renal Cell Carcinoma.

机构信息

Department of Urology, Renmin Hospital of Wuhan University, Hubei, China.

Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.

出版信息

Biomed Res Int. 2018 Oct 11;2018:9303486. doi: 10.1155/2018/9303486. eCollection 2018.

Abstract

. Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), usually is representative of metastatic heterogeneous neoplasm that links with poor prognosis, but the pathogenesis of ccRCC remains unclear. Currently, numerous evidences prove that long noncoding RNAs (lncRNAs) are considered as competing endogenous RNA (ceRNA) to participate in cellular processes of tumors. Therefore, to investigate the underlying mechanisms of ccRCC, the expression profiles of lncRNAs, miRNAs, and mRNAs were downloaded from the Cancer Genome Atlas (TCGA) database. A total of 1526 differentially expressed lncRNAs (DElncRNAs), 54 DEmiRNAs, and 2352 DEmRNAs were identified. To determine the connection of them, all DElncRNAs were input to the miRcode database. The results indicated that 85 DElncRNAs could connect with 9 DEmiRNAs in relation to our study. Then, databases of TargetScan and miRDB were used to search for targeted genes with reference to DEmiRNAs. The results showed that 203 out of 2352 targeted genes were identified in our TCGA set. Subsequently, ceRNA network was constructed according to Cytoscape and the targeted genes were functionally analyzed to elucidate the mechanisms of DEmRNAs. The results of survival analysis and regression analysis indicated that 6 DElncRNAs named COL18A1-AS1, WT1-AS, LINC00443, TCL6, AL356356.1, and SLC25A5-AS1 were significantly correlative with the clinical traits of ccRCC patients and could be served as predictors for ccRCC. Finally, these findings were validated by quantitative RT-PCR (qRT-PCR). Based on these discoveries, we believe that this identified ceRNA network will provide a novel perspective to elucidate ccRCC pathogenesis.

摘要

透明细胞肾细胞癌(ccRCC)是肾细胞癌(RCC)最常见的亚型,通常代表与预后不良相关的转移性异质性肿瘤,但 ccRCC 的发病机制尚不清楚。目前,大量证据表明,长链非编码 RNA(lncRNA)被认为是竞争性内源性 RNA(ceRNA),参与肿瘤的细胞过程。因此,为了研究 ccRCC 的潜在机制,从癌症基因组图谱(TCGA)数据库中下载了 lncRNA、miRNA 和 mRNA 的表达谱。共鉴定出 1526 个差异表达的 lncRNA(DElncRNA)、54 个 DEmiRNA 和 2352 个 DEmRNA。为了确定它们之间的联系,将所有 DElncRNA 输入到 miRcode 数据库中。结果表明,85 个 DElncRNA 可以与 9 个与我们的研究相关的 DEmiRNA 相连。然后,使用 TargetScan 和 miRDB 数据库搜索参照 DEmiRNA 的靶向基因。结果表明,在我们的 TCGA 集中,2352 个靶向基因中有 203 个被鉴定出来。随后,根据 Cytoscape 构建 ceRNA 网络,并对靶向基因进行功能分析,以阐明 DEmRNA 的机制。生存分析和回归分析的结果表明,6 个 DElncRNA,命名为 COL18A1-AS1、WT1-AS、LINC00443、TCL6、AL356356.1 和 SLC25A5-AS1,与 ccRCC 患者的临床特征显著相关,可以作为 ccRCC 的预测因子。最后,通过定量 RT-PCR(qRT-PCR)进行验证。基于这些发现,我们相信,该鉴定的 ceRNA 网络将为阐明 ccRCC 发病机制提供新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c22a/6201332/937975002fc9/BMRI2018-9303486.001.jpg

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