title: Epigenetic inactivation of microRNA-34b/c predicts poor disease-free survival in early-stage lung adenocarcinoma.
abstract: OBJECTIVE
  The microRNA-34b/c (miR-34b/c) is considered a tumor suppressor in different tumor types and a transcriptional target of TP53. The main objectives of this study were to investigate the clinical implications of miR-34b/c methylation in patients with early-stage lung adenocarcinoma and to determine the functional role of miR-34b/c re-expression in lung adenocarcinoma cell lines.
  
  
  METHODS
  Aberrant methylation and expression of miR-34b/c were assessed in 15 lung adenocarcinoma cell lines and a cohort of 140 early-stage lung adenocarcinoma. Lung adenocarcinoma cell lines were transfected with miR-34b/c and the effects upon cell proliferation, migration, invasion, and apoptosis were investigated.
  
  
  RESULTS
  Aberrant methylation of miR-34b/c was detected in 6 (40%) of 15 lung adenocarcinoma cell lines and 64 of 140 (46%) primary lung adenocarcinoma. Expression of miR-34b/c was significantly reduced in all methylated cell lines and primary tumors, especially with TP53 mutations. Patients with increased miR-34b/c methylation had significantly shorter disease-free and overall survival as compared to patients with unmethylated or low level of miR-34b/c methylation. Ectopic expression of miR-34b/c in lung adenocarcinoma cell lines decreased cell proliferation, migration, and invasion.
  
  
  CONCLUSIONS
  Epigenetic inactivation of miR-34b/c by DNA methylation has independent prognostic value in patients with early-stage lung adenocarcinoma. Reexpression of miR-34b/c leads to a less aggressive phenotype in lung adenocarcinoma cell lines.
authors.affiliation: Authors' Affiliations: Thoracic Surgery, Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan; and Translational Research Laboratory and Departments of Pathology, Thoracic Surgery, and Medical Oncology, Thoracic Oncology Multidisciplinary Unit, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Ernest
authors.initials: E
authors.lastname: Nadal
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
authors.forename: Marc
authors.initials: M
authors.lastname: Gallegos
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Daysha
authors.initials: D
authors.lastname: Ferrer-Torres
authors.forename: Anna
authors.initials: A
authors.lastname: Truini
authors.forename: Zhuwen
authors.initials: Z
authors.lastname: Wang
authors.forename: Jules
authors.initials: J
authors.lastname: Lin
authors.forename: Rishindra M
authors.initials: RM
authors.lastname: Reddy
authors.forename: Roger
authors.initials: R
authors.lastname: Llatjos
authors.forename: Ignacio
authors.initials: I
authors.lastname: Escobar
authors.forename: Juan
authors.initials: J
authors.lastname: Moya
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chang
authors.forename: Felipe
authors.initials: F
authors.lastname: Cardenal
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capellà
authors.forename: David G
authors.initials: DG
authors.lastname: Beer
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53