title: Silencing of miR-137 by aberrant promoter hypermethylation in surgically resected lung cancer.
abstract: BACKGROUND
  Recent studies demonstrated that miR-137 is downregulated in various tumors, and that it functions as a tumor suppressor. miR-137 could be silenced by its aberrant promoter hypermethylation. The purpose of this study was to investigate the significance of MIR137 promoter methylation on its expression in lung cancer.
  
  
  METHODS
  Lung cancer cell lines were treated with either a DNA methyltransferase inhibitor (5-azacytidine, AZA) and/or an HDAC inhibitor (trichostatin A, TSA) to determine whether miR-137 expression was reactivated. Paired lung tumor and adjacent non-tumor lung tissues were obtained (n=50). Quantitative methylation-specific PCR and bisulfite sequencing were used to analyze the methylation status of MIR137, and real-time RT-PCR was performed to analyze miR-137 expression.
  
  
  RESULTS
  miR-137 was reactivated by treatment with either AZA and/or TSA in lung cancer cell lines. Methylation-specific PCR showed increased MIR137 promoter methylation in lung tumors compared with adjacent non-tumor tissues, which was further validated by bisulfite sequencing. The expression of miR-137 was downregulated significantly in lung tumors, which was correlated with level of MIR137 promoter methylation inversely.
  
  
  CONCLUSIONS
  miR-137 downregulation was related to its promoter hypermethylation in lung cancer. Further studies are needed to assess its value as a prognostic factor and potential therapeutic applications in lung cancer.
authors.affiliation: The Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Nahyeon
authors.initials: N
authors.lastname: Kang
authors.affiliation: The Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Young Kyoon
authors.initials: YK
authors.lastname: Kim
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ie Ryung
authors.initials: IeR
authors.lastname: Yoo
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Dae Hee
authors.initials: DH
authors.lastname: Han
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yeon Sil
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kang
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Kyo Young
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jae Kil
authors.initials: JK
authors.lastname: Park
authors.affiliation: Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sook Whan
authors.initials: SW
authors.lastname: Sung
authors.affiliation: Department of Biostatistics, Clinical Research Coordinating Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Biostatistics, Clinical Research Coordinating Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyeon Woo
authors.initials: HW
authors.lastname: Yim
authors.affiliation: The Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; Multidisciplinary Team of Lung Cancer in Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: cmcksj@catholic.ac.kr.
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States.
authors.forename: Jong Y
authors.initials: JY
authors.lastname: Park
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D017422:Sequence Analysis, DNA
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D001374:Azacitidine
keywords: Lung cancer; MIR137; Promoter methylation; Silencing; Tumor suppressor; miR-137; microRNA