title: Long noncoding AGAP2-AS1 is activated by SP1 and promotes cell proliferation and invasion in gastric cancer.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Hepatopancreatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an City, People's Republic of China.
authors.forename: Fuzhen
authors.initials: F
authors.lastname: Qi
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of General Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People's Republic of China.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Digestive Endoscopy and Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People's Republic of China. jigzefy@163.com.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Fengqi
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Keming
authors.initials: K
authors.lastname: Wang
mesh_terms: D001706:Biopsy; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000032:analysis / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014158:Transcription, Genetic
chemical_list: C493956:CDKN1A protein, human; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D062085:RNA, Long Noncoding; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C000625008:long non-coding RNA AGAP2-AS1, human
keywords: AGAP2-AS1; E-cadherin; Invasion; Migration; P21; Proliferation; lncRNA