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Background: Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and cancer progression. Recently, the lncRNA AGAP2-AS1 was identified as an oncogenic lncRNA in human non-small cell lung cancer (NSCLC) and its elevated expression was linked to NSCLC development and progression. However, the expression pattern and molecular mechanism of AGAP2-AS1 in gastric cancer (GC) have not been characterized. Methods: Bioinformatic analysis was performed to determine AGAP2-AS1 expression levels in the GC and normal tissues using gene profiling data from the Gene Expression Omnibus. Quantitative real-time polymerase chain reaction was used to validate AGAP2-AS1 expression in the GC tissues/cell lines compared with that in the adjacent nontumorous tissues/normal epithelial cells. Loss- and gain-of-function approaches were performed to investigate the effect of AGAP2-AS1 on GC cell phenotypes. The effect of AGAP2-AS1 on cell proliferation was evaluated by MTT, colony formation, flow cytometry, and in vivo tumor formation assays. The effects of AGAP2-AS1 on cell migration and invasion were examined using Transwell assays. Chromatin immunoprecipitation, luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation were used to investigate the factors involved in AGAP2-AS1 dysregulation and the mechanism of action of AGAP2-AS1 in the GC cells. Results: AGAP2-AS1 was highly expressed in the GC tissues and cell lines, and patients with higher AGAP2-AS1 expression had a poorer prognosis and shorter overall survival. Furthermore, knockdown of AGAP2-AS1 significantly inhibited GC cell proliferation, migration, and invasion in vitro and tumor growth in vivo. AGAP2-AS1 overexpression promoted cell growth and invasion. In addition, the transcription factor SP1 activated AGAP2-AS1 expression in the GC cells. AGAP2-AS1 functions as an oncogenic lncRNA by interacting with LSD1 and EZH2 and suppressing CDKN1A (P21) and E-cadherin transcription. Conclusions: Taken together, these findings imply that AGAP2-AS1 upregulated by SP1 plays an important role in GC development and progression by suppressing P21 and E-cadherin, which suggests that AGAP2-AS1 is a potential diagnostic marker and therapeutic target for GC patients.
Qi, F., Liu, X., Wu, H., Yu, X., Wei, C., Huang, X., … Wang, K. (2017). Long noncoding AGAP2-AS1 is activated by SP1 and promotes cell proliferation and invasion in gastric cancer. Journal of Hematology and Oncology, 10(1). https://doi.org/10.1186/s13045-017-0420-4