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Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis
Neurogenic differentiation factor 1 (NeuroD1) is a transcription factor critical for promoting neuronal differentiation and maturation. NeuroD1 is involved in neuroblastoma and medulloblastoma; however, its molecular mechanism in promoting tumorigenesis remains unclear. Furthermore, the role of Neur...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942426/ https://www.ncbi.nlm.nih.gov/pubmed/31715070 http://dx.doi.org/10.1111/cas.14233 |
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author | Lei, Ke Li, Wenfang Huang, Can Li, Yanjun Alfason, Leader Zhao, Hezhao Miyagishi, Makoto Wu, Shourong Kasim, Vivi |
author_facet | Lei, Ke Li, Wenfang Huang, Can Li, Yanjun Alfason, Leader Zhao, Hezhao Miyagishi, Makoto Wu, Shourong Kasim, Vivi |
author_sort | Lei, Ke |
collection | PubMed |
description | Neurogenic differentiation factor 1 (NeuroD1) is a transcription factor critical for promoting neuronal differentiation and maturation. NeuroD1 is involved in neuroblastoma and medulloblastoma; however, its molecular mechanism in promoting tumorigenesis remains unclear. Furthermore, the role of NeuroD1 in non–neural malignancies has not been widely characterized. Here, we found that NeuroD1 is highly expressed in colorectal cancer. NeuroD1‐silencing induces the expression of p21, a master regulator of the cell cycle, leading to G(2)‐M phase arrest and suppression of colorectal cancer cell proliferation as well as colony formation potential. Moreover, NeuroD1‐mediated regulation of p21 expression occurs in a p53‐dependent manner. Through chromatin immunoprecipitation and point mutation analysis in the predicted NeuroD1 binding site of the p53 promoter, we found that NeuroD1 directly binds to the p53 promoter and suppresses its transcription, resulting in increased p53 expression in NeuroD1‐silenced colorectal cancer cells. Finally, xenograft experiments demonstrated that NeuroD1‐silencing suppresses colorectal cancer cell tumorigenesis potential by modulating p53 expression. These findings reveal NeuroD1 as a novel regulator of the p53/p21 axis, underscoring its importance in promoting non–neural malignancies. Furthermore, this study provides insight into the transcriptional regulation of p53. |
format | Online Article Text |
id | pubmed-6942426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69424262020-01-07 Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis Lei, Ke Li, Wenfang Huang, Can Li, Yanjun Alfason, Leader Zhao, Hezhao Miyagishi, Makoto Wu, Shourong Kasim, Vivi Cancer Sci Original Articles Neurogenic differentiation factor 1 (NeuroD1) is a transcription factor critical for promoting neuronal differentiation and maturation. NeuroD1 is involved in neuroblastoma and medulloblastoma; however, its molecular mechanism in promoting tumorigenesis remains unclear. Furthermore, the role of NeuroD1 in non–neural malignancies has not been widely characterized. Here, we found that NeuroD1 is highly expressed in colorectal cancer. NeuroD1‐silencing induces the expression of p21, a master regulator of the cell cycle, leading to G(2)‐M phase arrest and suppression of colorectal cancer cell proliferation as well as colony formation potential. Moreover, NeuroD1‐mediated regulation of p21 expression occurs in a p53‐dependent manner. Through chromatin immunoprecipitation and point mutation analysis in the predicted NeuroD1 binding site of the p53 promoter, we found that NeuroD1 directly binds to the p53 promoter and suppresses its transcription, resulting in increased p53 expression in NeuroD1‐silenced colorectal cancer cells. Finally, xenograft experiments demonstrated that NeuroD1‐silencing suppresses colorectal cancer cell tumorigenesis potential by modulating p53 expression. These findings reveal NeuroD1 as a novel regulator of the p53/p21 axis, underscoring its importance in promoting non–neural malignancies. Furthermore, this study provides insight into the transcriptional regulation of p53. John Wiley and Sons Inc. 2019-12-10 2020-01 /pmc/articles/PMC6942426/ /pubmed/31715070 http://dx.doi.org/10.1111/cas.14233 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Lei, Ke Li, Wenfang Huang, Can Li, Yanjun Alfason, Leader Zhao, Hezhao Miyagishi, Makoto Wu, Shourong Kasim, Vivi Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
title | Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
title_full | Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
title_fullStr | Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
title_full_unstemmed | Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
title_short | Neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
title_sort | neurogenic differentiation factor 1 promotes colorectal cancer cell proliferation and tumorigenesis by suppressing the p53/p21 axis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942426/ https://www.ncbi.nlm.nih.gov/pubmed/31715070 http://dx.doi.org/10.1111/cas.14233 |
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