title: Inhibition of microRNA-383 has tumor suppressive effect in human epithelial ovarian cancer through the action on caspase-2 gene.
abstract: BACKGROUND
  MicroRNAs are important cancer regulators. In this work, we examined the expression pattern and mechanistic implications of microRNA-383 (miR-383) in human epithelial ovarian cancer (EOC).
  
  
  METHODS
  Gene expression level of miR-383 was compared by qRT-PCR between EOC cell lines and normal ovarian epithelial cell line, and between clinical EOC tumors and adjacent non-tumor ovarian epithelial tissues. Endogenous miR-383 was downregulated through lentiviral infection. Its effects on regulating EOC proliferation, cell cycle, invasion and in vivo explant development were assessed. Possible downstream target of miR-383 in EOC, human caspase-2 gene (CASP2), was evaluated by luciferase assay and qRT-PCR. CASP2 was then genetically knocked down by siRNA to assess its functional relationship with miR-383 in regulating EOC development both in vitro and in vivo.
  
  
  RESULTS
  MiR-383 was overexpressed in both immortal EOC cell lines and human EOC tumors. In stably miR-383-downregulated EOC cell lines, cancer proliferation, cell cycle progression, invasion and in vivo explant development were significantly suppressed. CASP2 was confirmed to be downstream of miR-383 in EOC. SiRNA-mediated CASP2 downregulation had reverse relationship with miR-383 downregulation in regulating EOC development both in vitro and in vivo.
  
  
  CONCLUSIONS
  Inhibition of miR-383 has profound tumor suppressing effect on EOC development. And the functional regulation of miR-383 in EOC is very likely inversely associated with CASP2 gene.
authors: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China.
authors: Junbao
authors: J
authors: Liu
authors: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China; Department of Traditional Chinese Medicine, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China. Electronic address: yuchang.dou@aol.com.
authors: Yuchang
authors: Y
authors: Dou
authors: Department of Obstetrics and Gynecology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, PR China.
authors: Minjia
authors: M
authors: Sheng
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D053143:Caspase 2 / Q000096:biosynthesis / Q000235:genetics*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000517:prevention & control*
chemical_list: C558685:MIRN383 microRNA, human; D035683:MicroRNAs; C490360:CASP2 protein, human; D053143:Caspase 2; D003546:Cysteine Endopeptidases
keywords: CASP2; Cancer explant; Cancer proliferation; Epithelial ovarian cancer