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Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer

Colorectal cancer (CRC) is one of the most commonly diagnosed and leading causes of cancer mortality worldwide, and the prognosis of patients with CRC remains unsatisfactory. Basic transcription factor 3 (BTF3) is an oncogene and hazardous prognosticator in CRC. Although two distinct functional mech...

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Autores principales: Wang, Hantao, Xing, Junjie, Wang, Wei, Lv, Guifen, He, Haiyan, Lu, Yeqing, Sun, Mei, Chen, Haiyan, Li, Xu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905040/
https://www.ncbi.nlm.nih.gov/pubmed/33644029
http://dx.doi.org/10.3389/fcell.2020.601502
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author Wang, Hantao
Xing, Junjie
Wang, Wei
Lv, Guifen
He, Haiyan
Lu, Yeqing
Sun, Mei
Chen, Haiyan
Li, Xu
author_facet Wang, Hantao
Xing, Junjie
Wang, Wei
Lv, Guifen
He, Haiyan
Lu, Yeqing
Sun, Mei
Chen, Haiyan
Li, Xu
author_sort Wang, Hantao
collection PubMed
description Colorectal cancer (CRC) is one of the most commonly diagnosed and leading causes of cancer mortality worldwide, and the prognosis of patients with CRC remains unsatisfactory. Basic transcription factor 3 (BTF3) is an oncogene and hazardous prognosticator in CRC. Although two distinct functional mechanisms of BTF3 in different cancer types have been reported, its role in CRC is still unclear. In this study, we aimed to molecularly characterize the oncogene BTF3 and its targets in CRC. Here, we first identified the transcriptional targets of BTF3 by applying combined RNA-Seq and ChIP-Seq analysis, identifying CHD1L as a transcriptional target of BTF3. Thereafter, we conducted immunoprecipitation (IP)-MS and E3 ubiquitin ligase analysis to identify potential interacting targets of BTF3 as a subunit of the nascent-polypeptide-associated complex (NAC). The analysis revealed that BTF3 might also inhibit E3 ubiquitin ligase HERC2-mediated p53 degradation. Finally, miRNAs targeting BTF3 were predicted and validated. Decreased miR-497-5p expression is responsible for higher levels of BTF3 post-transcriptionally. Collectively, we concluded that BTF3 is an oncogene, and there may exist a transcription factor and NAC-related proteolysis mechanism in CRC. This study provides a comprehensive basis for understanding the oncogenic mechanisms of BTF3 in CRC.
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spelling pubmed-79050402021-02-26 Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer Wang, Hantao Xing, Junjie Wang, Wei Lv, Guifen He, Haiyan Lu, Yeqing Sun, Mei Chen, Haiyan Li, Xu Front Cell Dev Biol Cell and Developmental Biology Colorectal cancer (CRC) is one of the most commonly diagnosed and leading causes of cancer mortality worldwide, and the prognosis of patients with CRC remains unsatisfactory. Basic transcription factor 3 (BTF3) is an oncogene and hazardous prognosticator in CRC. Although two distinct functional mechanisms of BTF3 in different cancer types have been reported, its role in CRC is still unclear. In this study, we aimed to molecularly characterize the oncogene BTF3 and its targets in CRC. Here, we first identified the transcriptional targets of BTF3 by applying combined RNA-Seq and ChIP-Seq analysis, identifying CHD1L as a transcriptional target of BTF3. Thereafter, we conducted immunoprecipitation (IP)-MS and E3 ubiquitin ligase analysis to identify potential interacting targets of BTF3 as a subunit of the nascent-polypeptide-associated complex (NAC). The analysis revealed that BTF3 might also inhibit E3 ubiquitin ligase HERC2-mediated p53 degradation. Finally, miRNAs targeting BTF3 were predicted and validated. Decreased miR-497-5p expression is responsible for higher levels of BTF3 post-transcriptionally. Collectively, we concluded that BTF3 is an oncogene, and there may exist a transcription factor and NAC-related proteolysis mechanism in CRC. This study provides a comprehensive basis for understanding the oncogenic mechanisms of BTF3 in CRC. Frontiers Media S.A. 2021-02-11 /pmc/articles/PMC7905040/ /pubmed/33644029 http://dx.doi.org/10.3389/fcell.2020.601502 Text en Copyright © 2021 Wang, Xing, Wang, Lv, He, Lu, Sun, Chen and Li. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Wang, Hantao
Xing, Junjie
Wang, Wei
Lv, Guifen
He, Haiyan
Lu, Yeqing
Sun, Mei
Chen, Haiyan
Li, Xu
Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer
title Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer
title_full Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer
title_fullStr Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer
title_full_unstemmed Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer
title_short Molecular Characterization of the Oncogene BTF3 and Its Targets in Colorectal Cancer
title_sort molecular characterization of the oncogene btf3 and its targets in colorectal cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905040/
https://www.ncbi.nlm.nih.gov/pubmed/33644029
http://dx.doi.org/10.3389/fcell.2020.601502
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