title: Lentivirus-mediated RNA interference targeting the H19 gene inhibits cell proliferation and apoptosis in human choriocarcinoma cell line JAR.
abstract: BACKGROUND
  H19 is a paternally imprinted gene that has been shown to be highly expressed in the trophoblast tissue. Results from previous studies have initiated a debate as to whether noncoding RNA H19 acts as a tumor suppressor or as a tumor promotor in trophoblast tissue. In the present study, we developed lentiviral vectors expressing H19-specific small interfering RNA (siRNA) to specifically block the expression of H19 in the human choriocarcinoma cell line JAR. Using this approach, we investigated the impact of the H19 gene on the proliferation, invasion and apoptosis of JAR cells. Moreover, we examined the effect of H19 knockdown on the expression of insulin-like growth factor 2 (IGF2), hairy and enhancer of split homologue-1 (HES-1) and dual-specific phosphatase 5 (DUSP5) genes.
  
  
  RESULTS
  H19 knockdown inhibited apoptosis and proliferation of JAR cells, but had no significant impact on cell invasion. In addition, H19 knockdown resulted in significant upregulation of HES-1 and DUSP5 expression, but not IGF2 expression in JAR cells.
  
  
  CONCLUSIONS
  The finding that H19 downregulation could simultaneously inhibit proliferation and apoptosis of JAR cells highlights a putative dual function for H19 in choriocarcinoma and may explain the debate on whether H19 acts as a tumor suppressor or a tumor promotor in trophoblast tissue. Furthermore, upregulation of HES-1 and DUSP5 may mediate H19 downregulation-induced suppression of proliferation and apoptosis of JAR cells.
authors.affiliation: Department of Obstetrics and Gynecology, Daping Hospital, The Third Military Medical University, Chongqing 400042, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Yu
authors.forename: Kai
authors.initials: K
authors.lastname: Chang
authors.forename: Lin-Shan
authors.initials: LS
authors.lastname: Lu
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Han
authors.forename: Ying-Ru
authors.initials: YR
authors.lastname: Zheng
authors.forename: Yao-Hua
authors.initials: YH
authors.lastname: Yan
authors.forename: Ping
authors.initials: P
authors.lastname: Yi
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Guo
authors.forename: Yuan-Guo
authors.initials: YG
authors.lastname: Zhou
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology*; D054637:Dual-Specificity Phosphatases / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D034622:RNA Interference / Q000502:physiology*; D000072056:Transcription Factor HES-1; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D054637:Dual-Specificity Phosphatases; D018398:Homeodomain Proteins; D007335:Insulin-Like Growth Factor II; D009687:Nuclear Proteins; D000072056:Transcription Factor HES-1; D025521:Tumor Suppressor Proteins; C568299:HOTS protein, human; C078493:HES1 protein, human; C442320:DUSP5 protein, human