Department of Radiation Oncology, Anyang Cancer Hospital, The 4th Affiliated Hospital of Henan University of Science and Technology, Anyang, 455000, Henan Province, China.
Funct Integr Genomics. 2021 Jul;21(3-4):377-391. doi: 10.1007/s10142-021-00784-x. Epub 2021 Apr 16.
Esophageal carcinoma (EC) is a tremendous threat to human health and life worldwide. Long non-coding RNAs (lncRNAs) have been identified as crucial players in carcinomas including EC. An in-depth understanding on regulatory networks of lncRNAs contributes to the better management of EC. In this text, 2052 lncRNAs and 3240 mRNAs were found to be differentially expressed in 5 EC tumor tissues versus adjacent normal tissues by microarray analysis. Moreover, 297 carcinoma-related genes were screened out according to pathway and disease annotation analyses. In addition, 410 potential lncRNA-mRNA cis-regulation pairs and 395 lncRNA-mRNA trans-regulation pairs were screened out. Among these genes, 14 trans-regulated and 19 cis-regulated genes were found to be related with carcinomas. Additionally, 42 possible lncRNA-mRNA trans-regulation pairs and 26 cis-regulation pairs were found to be related with carcinomas. Also, 4 differentially expressed transcription factors in EC and lncRNAs possibly regulated by these transcription factors were screened out. Moreover, plenty of common upregulated or downregulated lncRNAs and mRNAs in EC were identified by comparative analysis for our microarray outcomes and previous high-throughput data. Furthermore, we demonstrated that ENST00000437781.1 knockdown inhibited cell proliferation and facilitated cell apoptosis by downregulating SIX homeobox 4 (SIX4) and ENST00000524987.1 knockdown had no influence on anoctamin 1 calcium activated chloride channel (ANO1) expression in EC cells. In conclusion, we identified some crucial lncRNAs and genes along with potential regulatory networks of lncRNAs/genes, deepening our understanding on pathogenesis of EC.
食管癌（EC）是全球范围内严重威胁人类健康和生命的疾病。长链非编码 RNA（lncRNA）已被确定为包括 EC 在内的多种癌症的关键调控因子。深入了解 lncRNA 的调控网络有助于更好地管理 EC。在本研究中，通过微阵列分析发现，5 例 EC 肿瘤组织与相邻正常组织相比，有 2052 个 lncRNA 和 3240 个 mRNA 表达差异。此外，根据通路和疾病注释分析筛选出 297 个癌相关基因。此外，筛选出 410 个潜在的 lncRNA-mRNA 顺式调控对和 395 个 lncRNA-mRNA 反式调控对。在这些基因中，有 14 个反式调控和 19 个顺式调控基因与癌症有关。此外，还发现了 42 个可能与 lncRNA-mRNA 反式调控有关的对和 26 个可能与 lncRNA-mRNA 顺式调控有关的对。此外，还筛选出 4 个在 EC 中差异表达的转录因子和可能受这些转录因子调控的 lncRNAs。此外，通过比较分析我们的微阵列结果和以前的高通量数据，鉴定出大量 EC 中差异表达的上调或下调的 lncRNA 和 mRNA。此外，我们还证明，ENST00000437781.1 的敲低通过下调 SIX 同源盒 4（SIX4）抑制了 EC 细胞的增殖并促进了细胞凋亡，而 ENST00000524987.1 的敲低对 anoctamin 1 钙激活氯离子通道（ANO1）的表达没有影响。总之，我们确定了一些关键的 lncRNA 和基因以及潜在的 lncRNA/基因调控网络，加深了我们对 EC 发病机制的理解。
