Ririno Honma1, Keisuke Goto2, Naoya Sakamoto1, Yohei Sekino1, Kazuhiro Sentani1, Naohide Oue1, Wataru Yasui3. 1. Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, 1-2-3 Kasumi Minami-ku, Hiroshima, 734-8551, Japan. 2. Cancer Biology Program, University of Hawaii Cancer Center, 701 Ilalo Street Suite 600, Honolulu, HI, 96813, USA. 3. 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.
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.
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 humancancer, 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.
Entities:
Keywords:
DNA methylation; Gastric cancer; Noncoding RNA; Transcribed ultraconserved region
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