title: Silencing the double-stranded RNA binding protein DGCR8 inhibits ovarian cancer cell proliferation, migration, and invasion.
abstract: OBJECTIVE
  To evaluate the role of DiGeorge Critical Region 8 (DGCR8), a key component of miRNA biogenesis pathway in ovarian cancer.
  
  
  METHODS
  The expression of DGCR8 in ovarian cancer was detected by immunostaining and DGCR8 knockdown in ovarian cancer cells was achieved using lentiviral shRNA. Differential expression of miRNAs was determined using Nanostring miRNA arrays and validated by real-time RT-PCR.
  
  
  RESULTS
  DGCR8 was highly expressed in ovarian cancer. Knockdown of DGCR8 expression inhibits cell proliferation, migration, and invasion, as well as sensitizes cells to apoptosis induced by the chemotherapeutic drug cisplatin. Cellular survival pathways including ERK1/2 mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT were attenuated in DGCR8 knockdown cells. DGCR8 knockdown results in dysregulated miRNA gene expression. miR-27b was identified as the most highly down-regulated miRNA in DGCR8 knockdown cells and promoted cell proliferation in ovarian cancer cells.
  
  
  CONCLUSIONS
  DGCR8 functions as an oncogene in ovarian cancer, which is in part mediated by miR-27b.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Guo
authors.forename: Peng
authors.initials: P
authors.lastname: Tian
authors.forename: Chuanhe
authors.initials: C
authors.lastname: Yang
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Liang
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Michelle
authors.initials: M
authors.lastname: Sims
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Pfeffer
authors.forename: Junming
authors.initials: J
authors.lastname: Yue
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009857:Oncogenes; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C474043:DGCR8 protein, human; C531388:MIRN27 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D002945:Cisplatin
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