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A genome‐wide analysis of long noncoding RNA profile identifies differentially expressed lncRNAs associated with Esophageal cancer

机译:对长非编码RNA谱进行全基因组分析可鉴定与食管癌相关的差异表达的lncRNA

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摘要

Esophageal cancer is one of the most common cancers and a leading cause of cancer‐related death worldwide. However, the mechanism of esophageal cancer pathogenesis remains poorly understood. Long noncoding RNAs (lncRNAs) dysregulation have been reported to involve in various human cancers, which highlights the potential of lncRNAs used as novel biomarkers for cancer diagnosis. Although more efforts have been made to identify novel lncRNAs signature in esophageal cancer, the expression pattern, prognostic value, and biological function of most lncRNAs in esophageal cancer still need to be systematically investigated. In this study, we comprehensively analyzed the expression profile of lncRNAs in more than 200 esophageal cancer patients tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We identified thousands of lncRNAs are differentially expressed in esophageal cancer tissues, and many of those lncRNAs expression are associated with patients overall survival or recurrence‐free survival time. Moreover, copy number variation analyses revealed that genomic loci copy number amplification or deletion might contribute to these lncRNAs dysregulation. Among these lncRNAs, DUXAP8 and LINC00460 were significantly upregulated, and GO enrichment analyses indicated that the two lncRNAs associated protein‐coding genes involve with many known biological processes, such as cell cycle and cell‐cell adherens junction. Further experimental validation revealed that knockdown of style="fixed-case">DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lnc style="fixed-case">RNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lnc style="fixed-case">RNAs.
机译:食道癌是世界上最常见的癌症之一,也是与癌症相关的死亡的主要原因。然而,对食道癌发病机理的研究仍知之甚少。长期的非编码RNA(lncRNA)失调已被报道与多种人类癌症有关,这突显了lncRNA作为新型生物标志物用于癌症诊断的潜力。尽管已经做出更多努力来鉴定食管癌中新的lncRNAs特征,但是大多数lncRNAs在食管癌中的表达模式,预后价值和生物学功能仍需要系统地研究。在这项研究中,我们全面分析了来自癌症基因组图谱(TCGA)和基因表达综合(GEO)的200多个食道癌患者组织样本中lncRNA的表达谱。我们发现食管癌组织中成千上万的lncRNAs差异表达,其中许多lncRNAs的表达与患者的整体生存或无复发生存时间有关。此外,拷贝数变异分析表明,基因组基因座拷贝数的扩增或缺失可能会导致这些lncRNA失调。在这些lncRNA中,DUXAP8和LINC00460被显着上调,GO富集分析表明,两个与lncRNA相关的蛋白编码基因涉及许多已知的生物学过程,例如细胞周期和细胞-细胞粘附连接。进一步的实验验证表明,敲除 style =“ fixed-case”> DUXAP 8可能会损害食管癌细胞的体外增殖和侵袭能力。综上所述,我们的发现确定了食管癌中异常表达的lnc style =“ fixed-case”> RNA s可能为鉴定新型食管癌相关lnc style =“ fixed-case “> RNA s。

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