1. The transcribed-ultraconserved regions in prostate and gastric cancer: DNA hypermethylation and microRNA-associated regulation.
- Author
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Goto K, Ishikawa S, Honma R, Tanimoto K, Sakamoto N, Sentani K, Oue N, Teishima J, Matsubara A, and Yasui W
- Subjects
- Adult, Aged, Aged, 80 and over, Azacitidine pharmacology, Cell Line, Tumor, Cell Proliferation genetics, Conserved Sequence genetics, DNA, Neoplasm genetics, Down-Regulation drug effects, Enzyme Inhibitors pharmacology, Female, Gene Expression Profiling methods, Humans, Male, Middle Aged, Promoter Regions, Genetic genetics, Prostatic Neoplasms pathology, Reverse Transcriptase Polymerase Chain Reaction, Stomach Neoplasms pathology, DNA Methylation, Gene Expression Regulation, Neoplastic, MicroRNAs genetics, Prostatic Neoplasms genetics, Stomach Neoplasms genetics
- 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.
- Published
- 2016
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