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Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation

Epigenetic alterations have been reported to play critical roles in the development of colorectal cancer (CRC). However, the biological function of the lysine-specific histone demethylase 1B (LSD2/KDM1B) in CRC is not well understood. Therefore, we investigated the characteristics of LSD2 in CRC. We...

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Autores principales: Cai, Shaoxin, Wang, Jinsi, Zeng, Wei, Cheng, Xuefei, Liu, Lihang, Li, Weihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425427/
https://www.ncbi.nlm.nih.gov/pubmed/32726297
http://dx.doi.org/10.18632/aging.103558
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author Cai, Shaoxin
Wang, Jinsi
Zeng, Wei
Cheng, Xuefei
Liu, Lihang
Li, Weihua
author_facet Cai, Shaoxin
Wang, Jinsi
Zeng, Wei
Cheng, Xuefei
Liu, Lihang
Li, Weihua
author_sort Cai, Shaoxin
collection PubMed
description Epigenetic alterations have been reported to play critical roles in the development of colorectal cancer (CRC). However, the biological function of the lysine-specific histone demethylase 1B (LSD2/KDM1B) in CRC is not well understood. Therefore, we investigated the characteristics of LSD2 in CRC. We observed significant upregulation of LSD2 in CRC tissue compared to that in normal colorectal tissue. LSD2 promotes CRC cell proliferation and inhibits cell apoptosis through cell cycle regulation, promoting CRC progression both in vitro and in vivo. We found that LSD2 performs these functions by inhibiting the p53-p21-Rb pathway. Finally, we found that LSD2 directly binds to p53 and represses p53 expression via H3K4me2 demethylation at the p53 promoter. Our results revealed that LSD2 acts as an oncogene by binding and inhibiting p53 activity in CRC. Thus, LSD2 may be a new molecular target for CRC treatment.
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spelling pubmed-74254272020-08-25 Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation Cai, Shaoxin Wang, Jinsi Zeng, Wei Cheng, Xuefei Liu, Lihang Li, Weihua Aging (Albany NY) Research Paper Epigenetic alterations have been reported to play critical roles in the development of colorectal cancer (CRC). However, the biological function of the lysine-specific histone demethylase 1B (LSD2/KDM1B) in CRC is not well understood. Therefore, we investigated the characteristics of LSD2 in CRC. We observed significant upregulation of LSD2 in CRC tissue compared to that in normal colorectal tissue. LSD2 promotes CRC cell proliferation and inhibits cell apoptosis through cell cycle regulation, promoting CRC progression both in vitro and in vivo. We found that LSD2 performs these functions by inhibiting the p53-p21-Rb pathway. Finally, we found that LSD2 directly binds to p53 and represses p53 expression via H3K4me2 demethylation at the p53 promoter. Our results revealed that LSD2 acts as an oncogene by binding and inhibiting p53 activity in CRC. Thus, LSD2 may be a new molecular target for CRC treatment. Impact Journals 2020-07-29 /pmc/articles/PMC7425427/ /pubmed/32726297 http://dx.doi.org/10.18632/aging.103558 Text en Copyright © 2020 Cai et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Cai, Shaoxin
Wang, Jinsi
Zeng, Wei
Cheng, Xuefei
Liu, Lihang
Li, Weihua
Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation
title Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation
title_full Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation
title_fullStr Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation
title_full_unstemmed Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation
title_short Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation
title_sort lysine-specific histone demethylase 1b (lsd2/kdm1b) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through lsd2-mediated h3k4me2 demethylation
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425427/
https://www.ncbi.nlm.nih.gov/pubmed/32726297
http://dx.doi.org/10.18632/aging.103558
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