title: LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation.
abstract: Although the prognosis of gastric cancer patients have a favorable progression, there are some patients with unusual patterns of locoregional and systemic recurrence. Therefore, a better understanding of early molecular events of the disease is needed. Current evidences demonstrate that long noncoding RNAs (lncRNAs) may be an important class of functional regulators involved in human gastric cancers development. Our previous studies suggest that HOTAIR contributes to gastric cancer development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we investigated the characteristic of the LncRNA FEZF1-AS1 in gastric cancer.
  
  
  
  QRT-PCR was used to detect the expression of FEZF1-AS1 in gastric cancer tissues and cells. MTT assays, clonogenic survival assays and nude mouse xenograft model were used to examine the tumorigenesis function of FEZF1-AS1 in vitro and in vivo. Bioinformatics analysis were used to select downstream target genes of FEZF1-AS1. Cell cycle analysis, ChIP, RIP,RNA Pulldown assays were examined to dissect molecular mechanisms.
  
  
  
  In this study, we reported that FEZF1-AS1, a 2564 bp RNA, was overexpressed in gastric cancer, and upregulated FEZF1-AS1 expression indicated larger tumor size and higher clinical stage; additional higher expression of FEZF1-AS1 predicted poor prognosis. Further experiments revealed that knockdown FEZF1-AS1 significantly inhibited gastric cancer cells proliferation by inducing G1 arrest and apoptosis, whereas endogenous expression FEZF1-AS1 promoted cell growth. Additionally, RIP assay and RNA-pulldown assay evidenced that FEZF1-AS1 could epigenetically repress the expression of P21 via binding with LSD1, the first discovered demethylase. ChIP assays demonstrated that LSD1 could directly bind to the promoter of P21, inducing H3K4me2 demethylation.
  
  
  
  In summary, these data demonstrated that FEZF1-AS1 could act as an "oncogene" for gastric cancer partly through suppressing P21 expression; FEZF1-AS1 may be served as a candidate prognostic biomarker and target for new therapies of gastric cancer patients.
authors.affiliation: Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yan-Wen
authors.initials: YW
authors.lastname: Liu
authors.affiliation: Department of Laboratory, Affiliated Chest Hospital of southeast University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of surgery, Affiliated the second hospital of Bengbu Medical College, Lianyungang, jiangsu, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Fen
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China. lyw0171@outlook.com.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu, People's Republic of China. wangcailian65@hotmail.com.
authors.forename: Cailian
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China. nyefygz@163.com.
authors.forename: Guozhong
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D000073398:Demethylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; D062085:RNA, Long Noncoding; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: FEZF1-AS1; Gastric cancer; H3K4me2; LSD1; P21