Department of Gastroenterology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.
Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Cancer Med. 2018 Aug;7(8):4181-4189. doi: 10.1002/cam4.1536. Epub 2018 Jun 21.
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 DUXAP8 could impair esophageal cancer cells proliferation and invasion in vitro. Taken together, our findings identified more aberrantly expressed lncRNAs in esophageal cancer that may provide a useful resource for identifying novel esophageal cancer associated lncRNAs.
食管癌是最常见的癌症之一,也是全球癌症相关死亡的主要原因。然而,食管癌发病机制的机制仍知之甚少。长链非编码 RNA(lncRNA)的失调已被报道参与多种人类癌症,这凸显了 lncRNA 作为癌症诊断新型生物标志物的潜力。尽管已经做出更多努力来鉴定食管癌中的新型 lncRNA 特征,但大多数 lncRNA 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)和基因表达综合数据库(GEO)的 200 多个食管癌患者组织样本中的 lncRNA 表达谱。我们鉴定了数千个在食管癌组织中差异表达的 lncRNA,其中许多 lncRNA 的表达与患者的总生存期或无复发生存时间相关。此外,拷贝数变异分析表明基因组位点的拷贝数扩增或缺失可能导致这些 lncRNA 的失调。在这些 lncRNA 中,DUXAP8 和 LINC00460 显著上调,GO 富集分析表明这两个 lncRNA 相关的蛋白编码基因涉及许多已知的生物学过程,如细胞周期和细胞-细胞黏附连接。进一步的实验验证表明,DUXAP8 的敲低可体外损害食管癌细胞的增殖和侵袭。总之,我们的研究结果确定了食管癌中更多异常表达的 lncRNA,它们可能为鉴定新型食管癌相关 lncRNA 提供有用的资源。