Journal
GASTRIC CANCER
Volume 20, Issue 6, Pages 960-969Publisher
SPRINGER
DOI: 10.1007/s10120-017-0714-9
Keywords
Gastric cancer; Noncoding RNA; Transcribed ultraconserved region; DNA methylation
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Funding
- Japan Society for the Promotion of Science [JP15H04713, JP16K08691, 26670175, JP16K15247]
- Grants-in-Aid for Scientific Research [16H06999] Funding Source: KAKEN
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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.
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