title: Expression and function of Uc.160+, a transcribed ultraconserved region, in gastric cancer.
abstract: BACKGROUND
  Transcribed ultraconserved regions (T-UCRs) are a novel class of noncoding RNAs that are highly conserved among the orthologous regions in most vertebrates. It has been reported that T-UCRs have distinct signatures in human cancers. We previously discovered the downregulation of T-UCR expression in gastric cancer (GC), indicating that T-UCRs could play an important role in GC biology. Uc.160+, a T-UCR reported to be downregulated in human cancer, has not been examined in GC.
  
  
  METHODS
  We analyzed the expression pattern of Uc.160+ in nonneoplastic and tumor tissues of the stomach by using uantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH), specifically focusing on the mechanism of transcriptional regulation and target genes that are regulated by T-UCRs. We also attempted to determine the effect of Uc.160+ expression on biological features of GC cell lines by Western blotting.
  
  
  RESULTS
  On the basis of the qRT-PCR and ISH results, Uc.160+ expression in adenoma and GC tissues was clearly downregulated compared with that in nonneoplastic mucosa tissues of the stomach. Cancer-specific DNA methylation in the promoter region of Uc.160 was observed by bisulfite genomic DNA sequencing analysis. The effect of DNA methylation on Uc.160+ expression was further confirmed by reporter gene assay. We also revealed that Uc.160+ inhibited the phosphorylation of Akt by regulating phosphatase and tensin homolog (PTEN) expression.
  
  
  CONCLUSIONS
  These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Ririno
authors.initials: R
authors.lastname: Honma
authors.affiliation: Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street Suite 600, Honolulu, HI, 96813, USA.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sekino
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sentani
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Naohide
authors.initials: N
authors.lastname: Oue
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan. wyasui@hiroshima-u.ac.jp.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000236:Adenoma / Q000235:genetics; D000368:Aged; D001483:Base Sequence; D017124:Conserved Sequence / Q000235:genetics; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D062085:RNA, Long Noncoding
keywords: DNA methylation; Gastric cancer; Noncoding RNA; Transcribed ultraconserved region