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Review Article | Open Access

The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities

Guanjun Yanga,c,d,, Changyun Lia,c,d, Fan Taoa,c,d, Yanjun Liua,c,d, Minghui Zhua,c,d, Yu Dua,c,d, Chenjie Feia,c,d, Qiusheng Sheb( ), Jiong Chena,c,d( )
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, Zhejiang 315211, China
School of Life Science and Engineering, Henan University of Urban Construction, Pingdingshan, Henan 467044, China
Laboratory of Biochemistry and Molecular Biology, School of Marine Sciences, Ningbo University, Ningbo, Zhejiang 315211, China
Key Laboratory of Aquacultural Biotechnology Ministry of Education, Ningbo University, Ningbo, Zhejiang 315211, China

Peer review under responsibility of Chongqing Medical University.

Show Author Information

Abstract

Lysine-specific demethylase 4 A (KDM4A, also named JMJD2A, KIA0677, or JHDM3A) is a demethylase that can remove methyl groups from histones H3K9me2/3, H3K36me2/3, and H1.4K26me2/me3. Accumulating evidence suggests that KDM4A is not only involved in body homeostasis (such as cell proliferation, migration and differentiation, and tissue development) but also associated with multiple human diseases, especially cancers. Recently, an increasing number of studies have shown that pharmacological inhibition of KDM4A significantly attenuates tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. Although there are several reviews on the roles of the KDM4 subfamily in cancer development and therapy, all of them only briefly introduce the roles of KDM4A in cancer without systematically summarizing the specific mechanisms of KDM4A in various physiological and pathological processes, especially in tumorigenesis, which greatly limits advances in the understanding of the roles of KDM4A in a variety of cancers, discovering targeted selective KDM4A inhibitors, and exploring the adaptive profiles of KDM4A antagonists. Herein, we present the structure and functions of KDM4A, simply outline the functions of KDM4A in homeostasis and non-cancer diseases, summarize the role of KDM4A and its distinct target genes in the development of a variety of cancers, systematically classify KDM4A inhibitors, summarize the difficulties encountered in the research of KDM4A and the discovery of related drugs, and provide the corresponding solutions, which would contribute to understanding the recent research trends on KDM4A and advancing the progression of KDM4A as a drug target in cancer therapy.

Keywords

Drug resistanceCancer therapyHistone demethylationJmjC domainKDM4A

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Genes & Diseases
Volume 11 Issue 2,
March 2024
Pages 645-663
DOI: 10.1016/j.gendis.2022.12.020
Cite this article:
Yang G, Li C, Tao F, et al. The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities. Genes & Diseases, 2024, 11(2): 645-663. https://doi.org/10.1016/j.gendis.2022.12.020

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Received: 28 November 2022
Accepted: 28 December 2022
Published: 23 March 2023
© 2023 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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