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Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers

SIMPLE SUMMARY: Histone demethylase JMJD2D is a multifunctional epigenetic factor coordinating androgen receptor activation, DNA damage repair, DNA replication, cell cycle regulation, and inflammation modulation. JMJD2D is also a well-established epigenetic facilitator in the progression of multiple...

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Autores principales: Chen, Qiang, Peng, Kesong, Mo, Pingli, Yu, Chundong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221006/
https://www.ncbi.nlm.nih.gov/pubmed/35740507
http://dx.doi.org/10.3390/cancers14122841
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author Chen, Qiang
Peng, Kesong
Mo, Pingli
Yu, Chundong
author_facet Chen, Qiang
Peng, Kesong
Mo, Pingli
Yu, Chundong
author_sort Chen, Qiang
collection PubMed
description SIMPLE SUMMARY: Histone demethylase JMJD2D is a multifunctional epigenetic factor coordinating androgen receptor activation, DNA damage repair, DNA replication, cell cycle regulation, and inflammation modulation. JMJD2D is also a well-established epigenetic facilitator in the progression of multiple malignant tumors, especially in colorectal cancer (CRC) and hepatocellular cancer (HCC). This review aims to summarize the mechanisms of JMJD2D in promoting CRC and HCC progression, which provides novel ideas for targeting JMJD2D in oncotherapy. JMJD2D promotes gene transcription by reducing H3K9 methylation and serves as a coactivator to enhance the activities of multiple carcinogenic pathways, including Wnt/β-catenin, Hedgehog, HIF1, JAK-STAT3, and Notch signaling; or acts as an antagonist of the tumor suppressor p53. ABSTRACT: Posttranslational modifications (PTMs) of histones are well-established contributors in a variety of biological functions, especially tumorigenesis. Histone demethylase JMJD2D (also known as KDM4D), a member of the JMJD2 subfamily, promotes gene transcription by antagonizing H3K9 methylation. JMJD2D is an epigenetic factor coordinating androgen receptor activation, DNA damage repair, DNA replication, and cell cycle regulation. Recently, the oncogenic role of JMJD2D in colorectal cancer (CRC) and hepatocellular cancer (HCC) has been recognized. JMJD2D serves as a coactivator of β-catenin, Gli1/2, HIF1α, STAT3, IRF1, TCF4, and NICD or an antagonist of p53 to promote the progression of CRC and HCC. In this review, we summarize the molecular mechanisms of JMJD2D in promoting the progression of CRC and HCC as well as the constructive role of its targeting inhibitors in suppressing tumorigenesis and synergistically enhancing the efficacy of anti-PD-1/PD-L1 immunotherapy.
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spelling pubmed-92210062022-06-24 Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers Chen, Qiang Peng, Kesong Mo, Pingli Yu, Chundong Cancers (Basel) Review SIMPLE SUMMARY: Histone demethylase JMJD2D is a multifunctional epigenetic factor coordinating androgen receptor activation, DNA damage repair, DNA replication, cell cycle regulation, and inflammation modulation. JMJD2D is also a well-established epigenetic facilitator in the progression of multiple malignant tumors, especially in colorectal cancer (CRC) and hepatocellular cancer (HCC). This review aims to summarize the mechanisms of JMJD2D in promoting CRC and HCC progression, which provides novel ideas for targeting JMJD2D in oncotherapy. JMJD2D promotes gene transcription by reducing H3K9 methylation and serves as a coactivator to enhance the activities of multiple carcinogenic pathways, including Wnt/β-catenin, Hedgehog, HIF1, JAK-STAT3, and Notch signaling; or acts as an antagonist of the tumor suppressor p53. ABSTRACT: Posttranslational modifications (PTMs) of histones are well-established contributors in a variety of biological functions, especially tumorigenesis. Histone demethylase JMJD2D (also known as KDM4D), a member of the JMJD2 subfamily, promotes gene transcription by antagonizing H3K9 methylation. JMJD2D is an epigenetic factor coordinating androgen receptor activation, DNA damage repair, DNA replication, and cell cycle regulation. Recently, the oncogenic role of JMJD2D in colorectal cancer (CRC) and hepatocellular cancer (HCC) has been recognized. JMJD2D serves as a coactivator of β-catenin, Gli1/2, HIF1α, STAT3, IRF1, TCF4, and NICD or an antagonist of p53 to promote the progression of CRC and HCC. In this review, we summarize the molecular mechanisms of JMJD2D in promoting the progression of CRC and HCC as well as the constructive role of its targeting inhibitors in suppressing tumorigenesis and synergistically enhancing the efficacy of anti-PD-1/PD-L1 immunotherapy. MDPI 2022-06-08 /pmc/articles/PMC9221006/ /pubmed/35740507 http://dx.doi.org/10.3390/cancers14122841 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chen, Qiang
Peng, Kesong
Mo, Pingli
Yu, Chundong
Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers
title Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers
title_full Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers
title_fullStr Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers
title_full_unstemmed Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers
title_short Histone Demethylase JMJD2D: A Novel Player in Colorectal and Hepatocellular Cancers
title_sort histone demethylase jmjd2d: a novel player in colorectal and hepatocellular cancers
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221006/
https://www.ncbi.nlm.nih.gov/pubmed/35740507
http://dx.doi.org/10.3390/cancers14122841
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