Clinical Laboratory, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
PLoS One. 2013 Sep 12;8(9):e73920. doi: 10.1371/journal.pone.0073920. eCollection 2013.
The majority of the human genome is transcribed and generates non-coding RNAs (ncRNAs) that fail to encode protein information. Long non-coding RNAs (lncRNAs) are emerging as a novel class of ncRNAs, but our knowledge about these ncRNAs is limited. Previously, our laboratory has identified that a lncRNA, Urothelial cancer associated 1 (UCA1), played an important role in bladder cancer. Despite the recent interest in UCA1 as a diagnostic marker for bladder cancer, little is known about its transcriptional regulation. To elucidate the regulation of UCA1 gene expression, we have characterized the human UCA1 gene promoter. A 2.0-kb fragment of its 5' flanking region was cloned into a luciferase reporter vector. Deletion and mutation analysis suggested that an Ets-2 binding site was critical for UCA1 gene promoter activity. Further analysis of this site by gel shifting, chromatin immune precipitation (ChIP), and co-transfection experiments showed that transcription factor Ets-2 directly bound to the UCA1 promoter region and stimulated UCA1 promoter activity in bladder cancer cells. Taking into account the anti-apoptosis function of Ets-2, our data suggested that Ets-2 regulates apoptosis process by regulating the expression of UCA1, moreover UCA1 may be involved in the activation of Akt signaling pathway by Ets-2 in bladder cancer cells.
人类基因组的大部分都被转录，并产生不编码蛋白质信息的非编码 RNA（ncRNA）。长链非编码 RNA（lncRNA）作为一类新型的 ncRNA 出现，但我们对这些 ncRNA 的了解还很有限。以前，我们实验室已经鉴定出一种 lncRNA，即尿路上皮癌相关 1（UCA1），在膀胱癌中发挥重要作用。尽管最近人们对 UCA1 作为膀胱癌的诊断标志物很感兴趣，但对其转录调控知之甚少。为了阐明 UCA1 基因表达的调控机制，我们对其启动子进行了研究。将其 5'侧翼区的 2.0kb 片段克隆到荧光素酶报告载体中。缺失和突变分析表明，Ets-2 结合位点对于 UCA1 基因启动子活性至关重要。通过凝胶迁移、染色质免疫沉淀（ChIP）和共转染实验对该位点的进一步分析表明，转录因子 Ets-2 直接结合到 UCA1 启动子区域，并刺激膀胱癌细胞中的 UCA1 启动子活性。考虑到 Ets-2 的抗凋亡功能，我们的数据表明，Ets-2 通过调节 UCA1 的表达来调节细胞凋亡过程，此外，UCA1 可能参与了 Ets-2 在膀胱癌细胞中对 Akt 信号通路的激活。
