title: MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf¹/cip¹).
abstract: OBJECTIVE
  MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and proliferation in several solid epithelial cancers. Enhancer of zeste homolog 2 (EzH2) appears to be a functional target of miR-101. We explore the role of miR-101 and its interaction with EzH2 in epithelial ovarian carcinoma (EOC).
  
  
  METHODS
  In situ hybridization (ISH) for miR-101 was performed on EOC patient tissues and normal controls. EOC cell lines were transfected with miR-101 and subjected to growth analysis and clonogenic assays. Cell motility was assessed by Boyden chamber and wound-healing assays. P21(waf1/cip1) and EzH2 interaction was assessed by Chromatin Immunoprecipitation (ChIP) assay in MDAH-2774 cells. SCID mice were assessed for tumor burden after injection with miR-101 or control vector-treated MDAH-2774 cells.
  
  
  RESULTS
  ISH analysis revealed a decrease in miR-101 expression in EOC compared with normal tissue. MiR-101 re-expression in EOC cell lines resulted in increased apoptosis, decreased cellular proliferation, invasiveness, and reduced growth of tumor xenografts. CHIP assays revealed that re-expression of miR-101 inhibited the interaction of EzH2 with p21(waf1/cip1) promoter.
  
  
  CONCLUSIONS
  MiR-101 re-expression appears to have antitumor effects, providing a better understanding of the role of miR-101 in EOC.
authors.affiliation: Laboratory of Surgical Oncology & Developmental Therapeutics Department of Surgery, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: Assaad
authors.initials: A
authors.lastname: Semaan
authors.forename: Aamer M
authors.initials: AM
authors.lastname: Qazi
authors.forename: Shelly
authors.initials: S
authors.lastname: Seward
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Chamala
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Bryant
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Kumar
authors.forename: Robert
authors.initials: R
authors.lastname: Morris
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Steffes
authors.forename: David L
authors.initials: DL
authors.lastname: Bouwman
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Munkarah
authors.forename: Donald W
authors.initials: DW
authors.lastname: Weaver
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gruber
authors.forename: Ramesh B
authors.initials: RB
authors.lastname: Batchu
mesh_terms: D000818:Animals; D017209:Apoptosis; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D063151:Polycomb Repressive Complex 2; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2