title: Interference of lysine-specific demethylase 1 inhibits cellular invasion and proliferation in vivo in gastric cancer MKN-28 cells.
abstract: BACKGROUND
  Lysine-specific demethylase 1(LSD1), the first identified histone demethylase, plays an important role in the epigenetic regulation of gene activation and repression. Up-regulated LSD1expression has been reported in several malignant tumors.Our aim, therefore, was to better understand the mechanisms underlying the upregulation of LSD1 in gastric cancer.
  
  
  METHODS
  We used lentiviral shRNA to knockdown LSD1 in the gastric cancer MKN-28 cell line. Cell proliferation was measured by MTT assay while cell apoptosis was assessed by Annexin V-FITC/PI double staining flow cytometry. The invasive potential of gastric cancer cells was determined by matrigel invasion assay. Protein expression was detected by Western blot. In vivo, the effect of knocking down LSD1 on tumor growth and protein expression in gastric cancer cells in nude mice was investigated.
  
  
  RESULTS
  LSD1 knockdown in MKN-28 cell lines resulted in increasing the activity of cisplatin in vitro and the inhibition of cancer cell proliferation and invasion, and induced cell apoptosis. The expression of TGF-β1, VEGF, Bcl-2, β-catenin, p-ERK and p-Smad 2/3 proteins was inhibited in LSD1 knockdown cells. Moreover, in an in vivo model of gastric cancer, LSD1 knockdown suppressed tumor growth and protein expression.
  
  
  CONCLUSIONS
  LSD1 knockdown affected the fuction of gastric cancer MKN-28 cell line. LSD1 may be a latent target in the diagnosis and therapy of gastric cancer.
authors.affiliation: Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, China.
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Sui
authors.affiliation: Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, China.
authors.forename: You-Hong
authors.initials: YH
authors.lastname: Jiang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of China Medical University, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, China. Electronic address: mengfandong@sina.com.
authors.forename: Fan-Dong
authors.initials: FD
authors.lastname: Meng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056466:Histone Demethylases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D056466:Histone Demethylases; C495195:KDM1A protein, human; D002945:Cisplatin
keywords: Cisplatin; Gastric cancer; LSD1; Lentivirus; shRNA