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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Autores principales: Yuki Kuwano, Kensei Nishida, Kazuhito Rokutan
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/dc353caf2da04beabca761a3929fbb4b
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spelling oai:doaj.org-article:dc353caf2da04beabca761a3929fbb4b2021-12-02T18:27:48ZOverexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression10.1038/s41598-021-88123-92045-2322https://doaj.org/article/dc353caf2da04beabca761a3929fbb4b2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88123-9https://doaj.org/toc/2045-2322Abstract 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.Yuki KuwanoKensei NishidaKazuhito RokutanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Yuki Kuwano
Kensei Nishida
Kazuhito Rokutan
Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression
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.
format article
author Yuki Kuwano
Kensei Nishida
Kazuhito Rokutan
author_facet Yuki Kuwano
Kensei Nishida
Kazuhito Rokutan
author_sort Yuki Kuwano
title 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_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_sort overexpression of the transcribed ultraconserved region uc.138 accelerates colon cancer progression
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/dc353caf2da04beabca761a3929fbb4b
work_keys_str_mv AT yukikuwano overexpressionofthetranscribedultraconservedregionuc138acceleratescoloncancerprogression
AT kenseinishida overexpressionofthetranscribedultraconservedregionuc138acceleratescoloncancerprogression
AT kazuhitorokutan overexpressionofthetranscribedultraconservedregionuc138acceleratescoloncancerprogression
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