title: Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung cancer.
abstract: BACKGROUND
  Aberrant DNA hypermethylation has been implicated as a component of an epigenetic mechanism that silences genes in cancers.
  
  
  METHODS
  We performed a genome-wide search to identify differentially methylated loci between 26 tumor and adjacent non-tumor paired tissues from same lung cancer patients using restriction landmark genomic scanning (RLGS) analysis. Among 229 loci which were hypermethylated in lung tumors as compared to adjacent non-tumor tissues, solute carrier family 5, member 8 (SLC5A8) was one of the hypermethylated genes, and known as a tumor suppressor gene which is silenced by epigenetic changes in various tumors. We investigated the significance of DNA methylation in SLC5A8 expression in lung cancer cell lines, and 23 paired tumor and adjacent non-tumor lung tissues by reverse transcription-PCR (RT-PCR), quantitative methylation specific PCR (QMSP) and bisulfite modified DNA sequencing analyses.
  
  
  RESULTS
  Reduced or lost expression of SLC5A8 was observed in 39.1% (9/23) of the tumor tissues as compared with paired adjacent non-tumor tissues. Bisulfite sequencing results of lung cancer cell lines and tissues which did not express SLC5A8 showed a densely methylated promoter region of SLC5A8. SLC5A8 was reactivated by treatment with DNA methyltransferase inhibitor, 5-Aza and/or HDAC inhibitor, trichostatin A (TSA) in lung cancer cell lines, which did not express SLC5A8. Hypermethylation was detected at the promoter region of SLC5A8 in primary lung tumor tissues as compared with adjacent non-tumor tissues (14/23, 60.9%).
  
  
  CONCLUSIONS
  These results suggest that DNA methylation in the SLC5A8 promoter region may suppress the expression of SLC5A8 in lung tumor.
authors.affiliation: Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States.
authors.forename: Jong Y
authors.initials: JY
authors.lastname: Park
authors.forename: Donghwa
authors.initials: D
authors.lastname: Kim
authors.forename: Mihi
authors.initials: M
authors.lastname: Yang
authors.forename: Hyun Y
authors.initials: HY
authors.lastname: Park
authors.forename: Sang Haak
authors.initials: SH
authors.lastname: Lee
authors.forename: Maria
authors.initials: M
authors.lastname: Rincon
authors.forename: Jenny
authors.initials: J
authors.lastname: Kreahling
authors.forename: Christoph
authors.initials: C
authors.lastname: Plass
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Smiraglia
authors.forename: Melvyn S
authors.initials: MS
authors.lastname: Tockman
authors.forename: Seung Joon
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D055106:Genome-Wide Association Study; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D027501:Monocarboxylic Acid Transporters; D011401:Promoter Regions, Genetic / Q000235:genetics; D013489:Suppression, Genetic
chemical_list: D027682:Cation Transport Proteins; D027501:Monocarboxylic Acid Transporters; C476760:SLC5A8 protein, human