title: MicroRNA-101 exerts tumor-suppressive functions in non-small cell lung cancer through directly targeting enhancer of zeste homolog 2.
abstract: BACKGROUND
  Overexpression of the enhancer of zeste homolog 2 (EZH2) protein has been found in broad range of cancer types, including non-small cell lung cancer (NSCLC). Nevertheless, the mechanisms by which EZH2 becomes overexpressed in NSCLC remain unclear. MicroRNAs (miRNAs) can regulate target gene expression through translational control. In this study, we investigate whether miRNA (miR-101) regulates EZH2 expression in NSCLC.
  
  
  METHODS
  We evaluated the expression of miR-101 and EZH2 in 20 matched NSCLC and adjacent nontumor lung tissues by reverse-transcriptase polymerase chain reaction and immunohistochemistry, respectively. Luciferase reporter assay was used to determine whether miR-101 directly targets EZH2. To assess the effect of miR-101 on NSCLC biological behavior, cell proliferation, invasion, and response to chemotherapy were analyzed using NSCLC cells transfected with miR-101 mimics or transfected with specific small interfering RNA to deplete EZH2 (small interfering RNA-EZH2).
  
  
  RESULTS
  Reduced expression of miR-101 was associated with overexpression of EZH2 in NSCLC tumor tissues. Transfection of miR-101 mimics significantly suppressed the activity of the luciferase reporter containing wild type but not mutant EZH2 3'-UTR and decreased EZH2 expression in NSCLC cell lines. Furthermore, enforced expression of miR-101 or knockdown of EZH2 led to reduced NSCLC cell proliferation and invasion and sensitized cancer cells to paclitaxel-mediated apoptosis through inducing expression of the proapoptotic protein Bim.
  
  
  CONCLUSIONS
  miR-101 inhibits cell proliferation and invasion and enhances paclitaxel-induced apoptosis in NSCLC cells, at least in part, by directly repressing EZH2 expression. Therapeutic strategies to rescue miR-101 expression or silence EZH2 may be beneficial to patients with NSCLC in the future.
authors.affiliation: Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Ji-Guang
authors.initials: JG
authors.lastname: Zhang
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Guo
authors.forename: Dong-Lei
authors.initials: DL
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D008156:Luciferases; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2