title: Oncogene LSD1 is epigenetically suppressed by miR-137 overexpression in human non-small cell lung cancer.
abstract: OBJECTIVE
  We examined the epigenetic regulation of microRNA-137 (miR-137) on lysine-specific demethylase 1 (KDM1A, or LSD1) induced oncogenic effects in NSCLC.
  
  
  METHODS
  NSCLC cell lines, A549 and H460 cells were transfected with a mammalian LSD1 overexpression plasmid. It's effects on endogenous KDM1A gene and LSD1 protein expressions were examined by qRT-PCR and western blot assays. NSCLC proliferation and migration were also examined by MTT proliferation and wound-scratch assays, respectively. In LSD1-overexpeseed NSCLC cells, lentiviral transfection was conducted to upregulated miR-137 expression. The subsequent effects of miR-137 upregulation on LSD1-mediated cancer regulations were also examined. In addition, key components of histone deacetylases-associated signaling pathways, including EZH2, HDAC1 and HDAC2 were also examined by western blot in LSD1-and miR-137-mediated NSCLC cells.
  
  
  RESULTS
  Mammalian LSD1 overexpression plasmid was efficient in upregulating KDM1A gene and LSD1 protein in A549 and H460 cells. It also exerted oncogenic effects in NSCLC by promoting cancer proliferation and migration. MiR-137 was inversely correlated with LSD1 in NSCLC, as lentivirus-mediated miR-137 upregulation suppressed KDM1A/LSD1 productions and inhibited proliferation or migration in LSD1-overexpressed A549 and H460 cells. Further western blot analysis demonstrated EZH2, HDAC1 and HDAC2 were activated by LSD1, but inhibited by miR-137 in NSCLC.
  
  
  CONCLUSIONS
  Oncogenic effects of LSD1 were reversely regulated by its upstream epigenetic modulator miR-137 in NSCLC. The interaction between LSD1 and miR-137 may very well involve the regulation on histone deacetylases-associated signaling pathways.
authors.affiliation: Department of Respiration, Liaocheng People's Hospital, Liaocheng, 252000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiration, Liaocheng People's Hospital, Liaocheng, 252000, China.
authors.forename: Xiujuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Respiration, Liaocheng People's Hospital, Liaocheng, 252000, China. Electronic address: b.yu3@aol.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
authors.affiliation: Department of Internal Medicine, Liaocheng Infection Hospital, Liaocheng, 252000, China.
authors.forename: Rongpeng
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Endocrinology, Yancheng City No.1 People's Hospital, Yancheng, 224001, China.
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Hao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D056466:Histone Demethylases; C495195:KDM1A protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: Biochemistry; LSD1; Lung cancer; MiR-137; NSCLC; Western blot