Ets-2 regulates cell apoptosis via the Akt pathway, through the regulation of urothelial cancer associated 1, a long non-coding RNA, in bladder cancer cells.
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.
Clinical Laboratory, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Wenjing
W
Wu
Shuwan
S
Zhang
Xu
X
Li
Mei
M
Xue
Sancheng
S
Cao
Wei
W
Chen
D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050787:Proto-Oncogene Protein c-ets-2 / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism*
D050787:Proto-Oncogene Protein c-ets-2; D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human; D051057:Proto-Oncogene Proteins c-akt