Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, P.R. China.
Oncol Rep. 2018 Aug;40(2):959-967. doi: 10.3892/or.2018.6476. Epub 2018 Jun 6.
Long non-coding RNAs (lncRNAs) make up a significant portion of transcripts that are not translated into proteins and lncRNAs were previously thought to be transcriptional noise. Recently, there has been increased interest in lncRNAs due to their diverse functions in human cancers. At present, lncRNAs are considered to be the main component of the competing endogenous RNA (ceRNA) network due to their regulatory role in protein-coding gene expression by acting as microRNA (miRNA) sponges. However, the function of the lncRNA-mediated ceRNA network in renal cell carcinoma remains unknown. To examine the specific mechanism, we compared the expression profiles of mRNAs, lncRNAs, and miRNAs between renal cell carcinoma tissues and non-tumor normal tissues using the Gene Expression Omnibus database. As a result, 5 lncRNAs were identified as aberrantly expressed and significantly correlated with the tumorigenesis and/or progression of renal cell carcinoma with the threshold value of absolute log2 fold change >1 and corrected P<0.05. Among the 5 dysregulated lncRNAs, 2 of them were prognostic biomarkers according to the overall survival analysis for patients with renal cell carcinoma. We successfully constructed a dysregulated lncRNA-associated ceRNA network, which included 4 renal cell carcinoma‑specific lncRNAs, 17 mRNAs and 2 miRNAs. In summary, the present study identified new lncRNA biomarkers and potential targets for renal cell carcinoma therapy. In particular, the novel ceRNA network identified in our study will be vital for understanding the regulatory mechanisms mediated by lncRNAs in the pathogenesis of renal cell carcinoma.
长链非编码 RNA（lncRNA）构成了不翻译成蛋白质的转录物的重要部分，以前认为 lncRNA 是转录噪音。最近，由于 lncRNA 在人类癌症中的多种功能，人们对 lncRNA 的兴趣有所增加。目前，lncRNA 被认为是竞争内源性 RNA（ceRNA）网络的主要组成部分，因为它们通过作为 microRNA（miRNA）海绵来调节蛋白质编码基因的表达。然而，lncRNA 介导的 ceRNA 网络在肾细胞癌中的功能仍不清楚。为了研究特定的机制，我们使用基因表达综合数据库比较了肾细胞癌组织和非肿瘤正常组织之间的 mRNA、lncRNA 和 miRNA 的表达谱。结果，鉴定出 5 个 lncRNA 表达异常，与肾细胞癌的发生和/或进展具有显著相关性，阈值为绝对 log2 倍数变化>1 和校正 P<0.05。在 5 个失调的 lncRNA 中，根据肾细胞癌患者的总生存分析，有 2 个是预后生物标志物。我们成功构建了一个失调的 lncRNA 相关 ceRNA 网络，其中包括 4 个肾细胞癌特异性 lncRNA、17 个 mRNA 和 2 个 miRNA。总之，本研究鉴定了新的 lncRNA 生物标志物和肾细胞癌治疗的潜在靶点。特别是，我们研究中鉴定的新型 ceRNA 网络对于理解 lncRNA 在肾细胞癌发病机制中介导的调节机制将至关重要。
