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利用微阵列和生物信息学分析研究透明细胞肾细胞癌患者血浆中长链非编码RNA和mRNA的失调情况

Dysregulation of Long Non-coding RNAs and mRNAs in Plasma of Clear Cell Renal Cell Carcinoma Patients Using Microarray and Bioinformatic Analysis.

作者信息

Zhang Bing, Chu Wei, Wen Feifei, Zhang Li, Sun Lixia, Hu Baoguang, Wang Jingjing, Su Qingguo, Mei Yanhui, Cao Jingyuan, Zheng Jing, Mou Xiaodong, Dong Hongliang, Lin Xiaoyan, Wang Nan, Ji Hong

机构信息

Department of Urology, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

Department of Pathology, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, China.

出版信息

Front Oncol. 2020 Nov 27;10:559730. doi: 10.3389/fonc.2020.559730. eCollection 2020.

Abstract

The roles of long non-coding RNAs (lncRNAs) in the diagnosis of clear cell renal cell carcinoma (ccRCC) are still not well-defined. We aimed to identify differentially expressed lncRNAs and mRNAs in plasma of ccRCC patients and health controls systematically. Expression profile of plasma lncRNAs and mRNAs in ccRCC patients and healthy controls was analyzed based on microarray assay. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-based approaches were used to investigate biological function and signaling pathways mediated by the differentially expressed mRNAs. SOCS2-AS1 was selected for validation using Real-Time PCR. The differentially expressed lncRNAs and mRNAs were further compared with E-MTAB-1830 datasets using Venn and the NetworkAnalyst website. The GEPIA and ULCAN websites were utilized for the evaluation of the expression level of differentially expressed mRNA and their association with overall survival (OS). A total of 3,664 differentially expressed lncRNAs were identified in the plasma of ccRCC patients, including 1,511 up-regulated and 2,153 down-regulated lncRNAs (fold change ≥2 and < 0.05), respectively. There were 2,268 differentially expressed mRNAs, including 932 up-regulated mRNAs and 1,336 down-regulated mRNAs, respectively (fold change ≥2 and < 0.05). Pathway analysis based on deregulated mRNAs was mainly involved in melanogenesis and Hippo signaling pathway ( < 0.05). In line with the lncRNA microarray findings, the SOCS2-AS1 was down-regulated in ccRCC plasma and tissues, as well as in cell lines. Compared with the E-MTAB-1830 gene expression profiles, we identified 18 lncRNAs and 87 mRNAs differently expressed in both plasma and neoplastic tissues of ccRCC. The expression of 10 mRNAs (, and ) was correlated with the overall survival (OS) rate in ccRCC patients based on the GEPIA and ULCAN websites. We firstly reported differentially expressed lncRNAs in ccRCC patients and healthy controls systemically. Several differentially expressed lncRNAs and mRNAs were identified, which might serve as diagnostic or prognostic markers. The biological function of these lncRNAs and mRNAs should be further validated. Our study may contribute to the future treatment of ccRCC and provide novel insights into cancer biology.

摘要

长链非编码RNA(lncRNA)在透明细胞肾细胞癌(ccRCC)诊断中的作用仍未明确界定。我们旨在系统地鉴定ccRCC患者和健康对照者血浆中差异表达的lncRNA和mRNA。基于微阵列分析对ccRCC患者和健康对照者血浆中的lncRNA和mRNA表达谱进行分析。采用基因本体论(GO)和基于京都基因与基因组百科全书(KEGG)通路的方法来研究差异表达mRNA介导的生物学功能和信号通路。选择SOCS2-AS1使用实时定量PCR进行验证。使用Venn和NetworkAnalyst网站将差异表达的lncRNA和mRNA与E-MTAB-1830数据集进行进一步比较。利用GEPIA和ULCAN网站评估差异表达mRNA的表达水平及其与总生存期(OS)的相关性。在ccRCC患者血浆中总共鉴定出3664个差异表达的lncRNA,其中分别有1511个lncRNA上调和2153个lncRNA下调(倍数变化≥2且<0.05)。有2268个差异表达的mRNA,分别包括932个上调的mRNA和1336个下调的mRNA(倍数变化≥2且<0.05)。基于失调mRNA的通路分析主要涉及黑色素生成和Hippo信号通路(<0.05)。与lncRNA微阵列结果一致,SOCS2-AS1在ccRCC血浆、组织以及细胞系中均下调。与E-MTAB-1830基因表达谱相比,我们在ccRCC的血浆和肿瘤组织中鉴定出18个lncRNA和87个mRNA差异表达。基于GEPIA和ULCAN网站,10个mRNA(……)的表达与ccRCC患者的总生存期(OS)率相关。我们首次系统地报道了ccRCC患者和健康对照者中差异表达的lncRNA。鉴定出了几种差异表达的lncRNA和mRNA,它们可能作为诊断或预后标志物。这些lncRNA和mRNA的生物学功能应进一步验证。我们的研究可能有助于ccRCC的未来治疗,并为癌症生物学提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b4c0/7729199/869eeb15e223/fonc-10-559730-g0001.jpg

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