title: Inhibition of telomerase activity by HDV ribozyme in cancers.
abstract: BACKGROUND
  Telomerase plays an important role in cell proliferation and carcinogenesis and is believed to be a good target for anti-cancer drugs. Elimination of template function of telomerase RNA may repress the telomerase activity.
  
  
  METHODS
  A pseudo-knotted HDV ribozyme (g.RZ57) directed against the RNA component of human telomerase (hTR) was designed and synthesized. An in vitro transcription plasmid and a eukaryotic expression plasmid of ribozyme were constructed. The eukaryotic expression plasmid was induced into heptocellular carcinoma 7402 cells, colon cancer HCT116 cells and L02 hepatocytes respectively. Then we determine the cleavage activity of ribozyme against human telomerase RNA component (hTR) both in vitro and in vivo, and detect telomerase activity continuously.
  
  
  RESULTS
  HDV ribozyme showed a specific cleavage activity against the telomerase RNA in vitro. The maximum cleavage ratio reached about 70.4%. Transfection of HDV ribozyme into 7402 cells and colon cancer cells HCT116 led to growth arrest and the spontaneous apoptosis of cells, and the telomerase activity dropped to 10% of that before.
  
  
  CONCLUSIONS
  HDV ribozyme (g.RZ57) is an effective strategy for gene therapy.
authors.affiliation: Department of Medicine, Beijing Friendship Hospital affiliated to Capital Medical University, Beijing 100050, PR China. ham69@sina.com
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lu
authors.forename: Junchao
authors.initials: J
authors.lastname: Gu
authors.forename: Dachuan
authors.initials: D
authors.lastname: Jin
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Gao
authors.forename: Mengbiao
authors.initials: M
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D003698:Hepatitis Delta Virus / Q000201:enzymology*; D022781:Hepatocytes / Q000201:enzymology; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology*; D009690:Nucleic Acid Conformation; D012313:RNA / Q000378:metabolism; D016337:RNA, Catalytic / Q000138:chemical synthesis / Q000235:genetics* / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D016337:RNA, Catalytic; D012313:RNA; D019098:Telomerase