Department of Neurology, Children's Hospital of Nanjing Medical University, Nanjing, China; Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Department of Environmental Genomics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
Gene. 2019 Apr 20;693:84-91. doi: 10.1016/j.gene.2019.01.028. Epub 2019 Feb 1.
Long noncoding RNAs (lncRNAs) play important roles in carcinogenesis. It is necessary to uncover the detailed pattern of comprehensive lncRNA expression in the genome during the development of gastric cancer (GC). We implemented lncRNA microarray analysis in 5 paired GC tissues to detect the lncRNA expression profile. Moreover, we set out to explore the biological function, clinical application and molecular basis of the aberrant lncRNA in GC. In addition, we used the high-throughput microarray to identify the target gene of the aberrant lncRNA. We found that FLJ22763, a novel lncRNA, had significantly lower expression in GC tissues. Decreased expression of FLJ22763 was positively correlated with a lower-level histological grade and the depth of invasion. The ectopic expression of lncRNA FLJ22763 significantly suppressed the biological malignant behavior of GC cells and inhibited xenograft tumor growth (both P < 0.001). Notably, FLJ22763 displayed a considerable predictive effect in the prognosis of GC (log-rank, P = 0.003). Furthermore, we found that FLJ22763 was negatively associated with ACLY, regulating the mRNA and protein levels of ACLY. Our findings suggested that FLJ22763 may act as a suppressor gene to regulate the expression of ACLY, and its down-expression may be an independent prognostic factor in patients with GC.
长链非编码 RNA（lncRNAs）在癌症发生中发挥重要作用。有必要揭示胃癌（GC）发展过程中基因组中全面 lncRNA 表达的详细模式。我们在 5 对 GC 组织中进行了 lncRNA 微阵列分析，以检测 lncRNA 的表达谱。此外，我们着手探索 GC 中异常 lncRNA 的生物学功能、临床应用和分子基础。此外，我们使用高通量微阵列来鉴定异常 lncRNA 的靶基因。我们发现 FLJ22763，一种新的 lncRNA，在 GC 组织中表达显著降低。FLJ22763 表达下调与组织学分级较低和浸润深度有关。lncRNA FLJ22763 的异位表达显著抑制 GC 细胞的生物学恶性行为并抑制异种移植肿瘤生长（均 P<0.001）。值得注意的是，FLJ22763 在 GC 的预后中显示出相当大的预测效果（对数秩，P=0.003）。此外，我们发现 FLJ22763 与 ACLY 呈负相关，调节 ACLY 的 mRNA 和蛋白水平。我们的研究结果表明，FLJ22763 可能作为一个抑制基因来调节 ACLY 的表达，其下调可能是 GC 患者的一个独立预后因素。
