The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy

Chen, Lijuan; Xu, Xin-Yang; Zhong, Xiao-Dan; Liu, Yanjun; Zhu, Minghui; Fan, Tao; Li, Changyun; She, Qiu-Sheng; Yang, Guan–Jun; Chen, Jiong

doi:10.1016/j.bioorg.2023.106409

Cited by 6 publications

(3 citation statements)

References 160 publications

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“…Some enzymes such as Jumonji C (JmjC) demethylases, ten-eleven-translocation (TET) enzymes, COX2, and HDACs are also metalloproteases and are invlvoled in modulating several chronic inflammatory diseases [( 5 , 7 ), Jin et al. and Wang et al.…”

Section: Othersmentioning

confidence: 99%

“…Mutiple chronic inflammatory diseases could even hijack various metalloproteases to promote and exacerbate inflammation ( 1 , 2 ). Numerous preclinical and clinical studies have shown that metalloprotease modulators, including lysine-specific demethyalses (KDMs) inhibitors ( 3 – 5 , 7 ), histone deacetylases (HDACs) inhibitors ( 8 ), and matrix metalloproteinases (MMPs) inhibitors ( 6 ), and a disintegrin and metalloproteinases (ADAMs) inhibitors ( 9 ), possess in vitro and in vivo anti–inflammatory activities. Therefore, understanding the roles of metalloproteinases in the immune system may potenitally uncover new targets for the diagnosis and treatment of chronic inflammatory diseases.…”

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confidence: 99%

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Editorial: Immunomodulatory role of metalloproteases in chronic inflammatory diseases

Yang

et al. 2023

Front. Immunol.

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Editorial on the Research TopicImmunomodulatory role of metalloproteases in chronic inflammatory diseases Metalloproteases are a diverse class of enzymes involved in the regulation of numerous pathological and physiological processes. Evidence has shown that metalloproteases could either directly or indirectly regulate the secretion of chemokines and the differentiation and/or activation of immune cells, thereby mediating many inflammatory and innate immune responses (1, 2). While different metalloproteases could have substantially different primary structure, their active center which contains metal ions (e.g. iron, zinc, cobalt, nickel ions) is relatively conservative. Metalloprotease relies on metal ions to maintain its catalytic function. Studies have shown that metal chelators such as EDTA could completely inactivate metalloproteases (3-6; Liu et al.). Under inflammatory conditions, metalloproteases are constitutively activated or deactivated in multiple immune-or non-immune cells and could contribute to a variety of inflammatory diseases, such as rheumatoid arthritis (RA) (Li et al.), chronic enteritis (Deng et al. and Mei et al.), allergic dieseases (Wang and Wang and Bendavid et al.), diabetes (Chen et al.), and cancers (He et al.), etc. Mutiple chronic inflammatory diseases could even hijack various metalloproteases to promote and exacerbate inflammation (1, 2). Numerous preclinical and clinical studies have shown that metalloprotease modulators, including lysine-specific demethyalses (KDMs) inhibitors (3-5, 7), histone deacetylases (HDACs) inhibitors (8), and matrix metalloproteinases (MMPs) inhibitors (6), and a disintegrin and metalloproteinases (ADAMs) inhibitors (9), possess in vitro and in vivo anti-inflammatory activities. Therefore, understanding the roles of metalloproteinases in the immune system may potenitally uncover new targets for the diagnosis and treatment of chronic inflammatory diseases.

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Section: Othersmentioning

confidence: 99%

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confidence: 99%

Editorial: Immunomodulatory role of metalloproteases in chronic inflammatory diseases

Yang

et al. 2023

Front. Immunol.

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“…KDMs consist of two classes of proteins of over 30 members, including the (i) flavin-dependent monoamine oxidases (LSD), and (ii) the Fe(II)-and α-ketoglutarate (2OG)-dependent oxygenases that possess a conserved catalytic Jumonji C domain (JmjC) [16]. Many KDMs members, such as LSD1, KDM4A/B/C/D, KDM6A, and KDM7A, are associated with BC progress in a subtype/ content-dependent manner, and inhibitors targeting them have been extensively developed [16][17][18][19][20][21]. KDM5, also known as JARID1 (jumonji domain ARID-containing protein), belongs to the JmjC family and comprises the four members KDM5A/B/C/D, which are encoded in the human genome at loci 12p13.33, 1q32.1, Xp11.22, and Yq11.223.1, respectively.…”

Section: Introductionmentioning

confidence: 99%

KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges

Li,

Wang,

Leung

et al. 2024

Mol Cancer

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Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations in the rates of progression-free disease and overall survival of patients. However, the treatment of BC still faces challenges, particularly in terms of drug resistance and recurrence. The study of epigenetics has provided new ideas for treating BC. Targeting aberrant epigenetic factors with inhibitors represents a promising anticancer strategy. The KDM5 family includes four members, KDM5A, KDM5B, KDM5C, and KDMD, all of which are Jumonji C domain-containing histone H3K4me2/3 demethylases. KDM5 proteins have been extensively studied in BC, where they are involved in suppressing or promoting BC depending on their specific upstream and downstream pathways. Several KDM5 inhibitors have shown potent BC inhibitory activity in vitro and in vivo, but challenges still exist in developing KDM5 inhibitors. In this review, we introduce the subtypes of BC and their current therapeutic options, summarize KDM5 family context-specific functions in the pathobiology of BC, and discuss the outlook and pitfalls of KDM5 inhibitors in this disease.

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Lysine-specific demethylase 7A (KDM7A): A potential target for disease therapy

Li,

Liu,

Tao

et al. 2023

Biochemical Pharmacology

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The role of lysine-specific demethylase 6A (KDM6A) in tumorigenesis and its therapeutic potentials in cancer therapy

Cited by 6 publications

References 160 publications

Editorial: Immunomodulatory role of metalloproteases in chronic inflammatory diseases

Editorial: Immunomodulatory role of metalloproteases in chronic inflammatory diseases

KDM5 family as therapeutic targets in breast cancer: Pathogenesis and therapeutic opportunities and challenges

Lysine-specific demethylase 7A (KDM7A): A potential target for disease therapy

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