Clinical Research Center, People's Hospital of Zhengzhou, 33 Yellow River Road, Zhengzhou, Henan 45003, China.
Int J Genomics. 2013;2013:480534. doi: 10.1155/2013/480534. Epub 2013 Oct 7.
Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the "cancer initiatome." Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC). We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.
肿瘤发生是一个复杂的动态生物学过程,包括多个遗传和表观遗传改变、非编码 RNA 的异常表达以及编码基因表达谱的变化。我们将这些基因组空间中的扰动集合称为“癌症起始组”。长非编码 RNA(lncRNA)在基因组中广泛转录,它们在染色质重塑和基因表达中具有关键的调节功能。lncRNA 的表达在发育和疾病状态(包括癌症)中存在时空变化。一些失调的 lncRNA 已在癌症中进行了研究,但 lncRNA 在癌症起始组中的作用仍知之甚少,尤其是在食管鳞状细胞癌(ESCC)中。我们对 ESCC 及其匹配的相邻非肿瘤正常组织中的 lncRNA 和编码 RNA 的表达进行了全基因组筛选。我们鉴定了 ESCC 中相对于其匹配的正常组织对照的差异表达的 lncRNA 和编码 RNA,并使用聚合酶链反应分析进行了验证。此外,我们鉴定了在 ESCC 中与差异表达的编码 RNA 共定位和共表达的差异表达 lncRNA,结果表明 lncRNA 和邻近编码基因之间存在潜在的相互作用,影响醚脂代谢,这种相互作用可能有助于 ESCC 的发生。这些数据为食管鳞状细胞癌的潜在新型基因组生物标志物提供了有力证据。