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The transcribed-ultraconserved regions in prostate and gastric cancer: DNA hypermethylation and microRNA-associated regulation

Oncogene volume 35, pages 3598–3606 (2016)Cite this article

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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.

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Acknowledgements

We thank Mr Shinichi Norimura for his excellent technical assistance. This work was carried out with the kind cooperation of the Research Center for Molecular Medicine of the Faculty of Medicine of Hiroshima University. We also thank the Analysis Center of Life Science of Hiroshima University for the use of their facilities. This work was supported, in part, by grants-in-aid for Cancer Research from the Ministry of Education, Culture, Science, Sports and Technology of Japan, and, in part, by a grant-in-aid for the Third Comprehensive. 10-Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, by the National Institute of Biomedical Innovation (Program for Promotion of Fundamental Studies in Health Sciences), and by the National Cancer Center Research and Development Fund.

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Authors and Affiliations

  1. Department of Molecular Pathology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

    K Goto, N Sakamoto, K Sentani, N Oue & W Yasui

  2. Department of Urology, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

    K Goto, J Teishima & A Matsubara

  3. School of Medicine, Hiroshima University, Hiroshima, Japan

    S Ishikawa & R Honma

  4. Department of Radiation Medicine, Hiroshima University Research Institute for Radiation Biology and Medicine, Hiroshima, Japan

    K Tanimoto

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  1. K Goto
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  2. S Ishikawa
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Correspondence to W Yasui.

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Goto, K., Ishikawa, S., Honma, R. et al. The transcribed-ultraconserved regions in prostate and gastric cancer: DNA hypermethylation and microRNA-associated regulation. Oncogene 35, 3598–3606 (2016). https://doi.org/10.1038/onc.2015.445

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