Expression and function of Uc.160+, a transcribed ultraconserved region, in gastric cancer
- 223 Downloads
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.
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.
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.
These results indicate that Uc.160+ could possibly have a tumor suppressive role in GC.
KeywordsGastric cancer Noncoding RNA Transcribed ultraconserved region DNA methylation
We thank Shinichi Norimura for excellent technical assistance. We thank the Analysis Center of Life Science, Hiroshima University, for the use of its facilities. This work was supported by Grants-in-Aid for Scientific Research (JP15H04713, JP16K08691) and Grants-in-Aid for Challenging Exploratory Research (26670175, JP16K15247) from the Japan Society for the Promotion of Science.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Human rights statement and informed consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or substitute for it was obtained from all patients for their being included in the study.