Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression
Abstract Ultraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-04-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-88123-9 |
| _version_ | 1818572898306097152 |
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| author | Yuki Kuwano Kensei Nishida Kazuhito Rokutan |
| author_facet | Yuki Kuwano Kensei Nishida Kazuhito Rokutan |
| author_sort | Yuki Kuwano |
| collection | DOAJ |
| description | Abstract Ultraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138) that spans exon 2 and its neighboring introns. TRA2B4 RNA is the only transcript that contains the whole exon 2 among five spliced TRA2B RNA variants (TRA2B1-5). TRA2B4 is upregulated in colon cancer cell lines, although it is not translated to Tra2β protein because of its nuclear retention. Nevertheless, the clinical significance and biological functions of uc.138 in colon cancer cells remain unclear. In this study, RNA in situ hybridization showed that TRA2B4 was predominantly overexpressed in the nucleus of colon adenocarcinoma and adenoma. Overexpression of TRA2B4 in colon cancer HCT116 cells promoted cell proliferation by changing the expression of G2/M-related cell cycle regulators. Moreover, TRA2B4 increased migration and cell viability in a uc.138 sequence-dependent manner. TRA2B4 significantly enhanced tumorigenesis in vivo. Taken together, uc.138 encoded in TRA2B4 plays an oncogenic role in tumor progression and may become a potential biomarker and therapeutic target in colon cancer. |
| first_indexed | 2024-12-15T00:03:48Z |
| format | Article |
| id | doaj.art-dc353caf2da04beabca761a3929fbb4b |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-15T00:03:48Z |
| publishDate | 2021-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dc353caf2da04beabca761a3929fbb4b2022-12-21T22:42:49ZengNature PortfolioScientific Reports2045-23222021-04-0111111210.1038/s41598-021-88123-9Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progressionYuki Kuwano0Kensei Nishida1Kazuhito Rokutan2Department of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolDepartment of Pathophysiology, Institute of Biomedical Sciences, Tokushima University Graduate SchoolAbstract Ultraconserved regions (UCRs) are 481 genomic sequences with 100% identity across humans, rats, and mice. Increasing evidence suggests that non-coding RNAs transcribed from UCRs are involved in various diseases, especially cancers. The human transformer 2β gene (TRA2B) encodes a UCR (uc.138) that spans exon 2 and its neighboring introns. TRA2B4 RNA is the only transcript that contains the whole exon 2 among five spliced TRA2B RNA variants (TRA2B1-5). TRA2B4 is upregulated in colon cancer cell lines, although it is not translated to Tra2β protein because of its nuclear retention. Nevertheless, the clinical significance and biological functions of uc.138 in colon cancer cells remain unclear. In this study, RNA in situ hybridization showed that TRA2B4 was predominantly overexpressed in the nucleus of colon adenocarcinoma and adenoma. Overexpression of TRA2B4 in colon cancer HCT116 cells promoted cell proliferation by changing the expression of G2/M-related cell cycle regulators. Moreover, TRA2B4 increased migration and cell viability in a uc.138 sequence-dependent manner. TRA2B4 significantly enhanced tumorigenesis in vivo. Taken together, uc.138 encoded in TRA2B4 plays an oncogenic role in tumor progression and may become a potential biomarker and therapeutic target in colon cancer.https://doi.org/10.1038/s41598-021-88123-9 |
| spellingShingle | Yuki Kuwano Kensei Nishida Kazuhito Rokutan Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression Scientific Reports |
| title | Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression |
| title_full | Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression |
| title_fullStr | Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression |
| title_full_unstemmed | Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression |
| title_short | Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression |
| title_sort | overexpression of the transcribed ultraconserved region uc 138 accelerates colon cancer progression |
| url | https://doi.org/10.1038/s41598-021-88123-9 |
| work_keys_str_mv | AT yukikuwano overexpressionofthetranscribedultraconservedregionuc138acceleratescoloncancerprogression AT kenseinishida overexpressionofthetranscribedultraconservedregionuc138acceleratescoloncancerprogression AT kazuhitorokutan overexpressionofthetranscribedultraconservedregionuc138acceleratescoloncancerprogression |