• Mingde Huang, Jiakai Hou, Yunfei Wang, Min Xie, Chenchen Wei, Fengqi Nie, Zhaoxia Wang, and Ming Sun.
• Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, People's Republic of China; Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
• Mol. Ther. 2017 Apr 5; 25 (4): 1014-1026.

AbstractLong noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the biological function of these molecules and the mechanisms responsible for their alteration in gastric cancer (GC) are not fully understood. In this study, we found that lncRNA LINC00673 is significantly upregulated in gastric cancer. Knockdown of LINC00673 inhibited cell proliferation and invasion and induced cell apoptosis, whereas LINC00673 overexpression had the opposite effect. Online transcription factor binding site prediction analysis showed that there are SP1 binding sites in the LINC00673 promoter region. Next, luciferase reporter and chromatin immunoprecipitation (ChIP) assays provided evidence that SP1 could bind directly to the LINC00673 promoter region and activate its transcription. Moreover, mechanistic investigation showed that CADM4, KLF2, and LATS2 might be the underlying targets of LINC00673 in GC cells, and RNA immunoprecipitation, RNA pull-down, and ChIP assays showed that LINC00673 can interact with EZH2 and LSD1, thereby repressing KLF2 and LATS2 expression. Taken together, these findings show that SP1-activated LINC00673 exerts an oncogenic function that promotes GC development and progression, at least in part, by functioning as a scaffold for LSD1 and EZH2 and repressing KLF2 and LATS2 expression.Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

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