title: The transcribed-ultraconserved regions in prostate and gastric cancer: DNA hypermethylation and microRNA-associated regulation.
abstract: The transcribed-ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs, which are absolutely conserved (100%) between the orthologous regions of the human, rat and mouse genomes. Previous studies have described that several T-UCRs show differential expressions in cancers and might be involved in cancer development. We investigated the transcriptional levels of representative 26 T-UCRs and determined the regions that were differently expressed in prostate cancer (PCa) and gastric cancer (GC). A quantitative reverse transcription-polymerase chain reaction analysis revealed the downregulation of Uc.158+A expression by a DNA methylation-associated mechanism, which was restored by 5-Aza-dC (5-aza-2'-deoxycytidine) treatment. Bisulfite genomic sequencing using cell lines and tissue samples demonstrated cancer-specific CpG hypermethylation in both GC and PCa. However, Uc.416+A was only overexpressed in GC and we identified an miR-153 binding site in the possible regulatory region of Uc.416+A using online databases. Along with a forced expression or knockdown of miR-153 in MKN-74 GC cells, the transcriptional levels of Uc.416+A were significantly disturbed. A luciferase reporter gene assay supported the direct regulation of Uc.416+A expression by miR-153. Furthermore, Uc.416+A was associated with cell growth through the regulation of IGFBP6 (insulin-like growth factor-binding protein 6) in GC. These findings suggest an oncogenic role of Uc.416+A in GC, which suggests that our approach would provide new insights into functional studies of T-UCRs in cancer biology.
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.|Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.affiliation: School of Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: School of Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Honma
authors.affiliation: Department of Radiation Medicine, Hiroshima University Research Institute for Radiation Biology and Medicine, Hiroshima Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanimoto
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sentani
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Oue
authors.affiliation: Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Teishima
authors.affiliation: Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsubara
authors.affiliation: Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Yasui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D035683:MicroRNAs; D001374:Azacitidine