JARID1 Histone Demethylases: Emerging Targets in Cancer

Harmeyer, Kayla M.; Facompre, Nicole D.; Herlyn, Meenhard; Basu, Devraj

doi:10.1016/j.trecan.2017.08.004

Cited by 85 publications

(72 citation statements)

References 130 publications

(153 reference statements)

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“…Convincing documents demonstrated that histone demethylases involve in different cellular procedures such as carcinogenesis, cell fate selection, and cell differentiation [120][121][122]. Currently, the increasing trend of documents showed the essential contribution of histone demethylases such as JARID1, KDM4, LSD1, KDM6B, KDM6A, KMD3, KDM5, and Jumonji domain-consisting of protein 6 (JMJD6) to the cancer stem cell phenotype in several kinds of cancers [61,[123][124][125][126][127][128][129][130]. JMJD6 has been represented as a new molecular modulator of OCSCs [61].…”

Section: Epigenetic Regulators and Oral Cancer Stem Cells Histone Demmentioning

confidence: 99%

Cancer stem cells and oral cancer: insights into molecular mechanisms and therapeutic approaches

2020

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Cancer stem cells (CSCs) have been identified as a little population of cancer cells, which have features as the same as the cells normal stem cells. There is enough knowledge of the CSCs responsibility for metastasis, medicine resistance, and cancer outbreak. Therefore, CSCs control possibly provides an efficient treatment intervention inhibiting tumor growth and invasion. In spite of the significance of targeting CSCs in treating cancer, few study comprehensively explored the nature of oral CSCs. It has been showed that oral CSCs are able to contribute to oral cancer progression though activation/inhibition a sequences of cellular and molecular pathways (microRNA network, histone modifications and calcium regulation). Hence, more understanding about the properties of oral cancers and their behaviors will help us to develop new therapeutic platforms. Head and neck CSCs remain a viable and intriguing option for targeted therapy. Multiple investigations suggested the major contribution of the CSCs to the metastasis, tumorigenesis, and resistance to the new therapeutic regimes. Therefore, experts in the field are examining the encouraging targeted therapeutic choices. In spite of the advancements, there are not enough information in this area and thus a magic bullet for targeting and eliminating the CSCs deviated us. Hence, additional investigations on the combined therapies against the head and neck CSCs could offer considerable achievements. The present research is a review of the recent information on oral CSCs, and focused on current advancements in new signaling pathways contributed to their stemness regulation. Moreover, we highlighted various therapeutic approaches against oral CSCs.

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Section: Epigenetic Regulators and Oral Cancer Stem Cells Histone Demmentioning

confidence: 99%

Cancer stem cells and oral cancer: insights into molecular mechanisms and therapeutic approaches

2020

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“…They are overexpressed in a number of different cancers including breast, ovarian and lung, and their expression correlates with both proliferation rate and propensity for metastatic invasion (HAYAMI et al 2010;HOU et al 2012;TENG et al 2013;YAMAMOTO et al 2014;WANG et al 2015;FENG et al 2017;HUANG et al 2018). The link between the X-linked KDM5C gene and cancer is less straight-forward, as it has both oncogenic and tumor suppressive activities in tissue-dependent manner (HARMEYER et al 2017). The Y-linked KDM5D gene is a tumor suppressor and prognostic indicator of poor outcome in cases of prostate cancer (KOMURA et al 2016;LI et al 2016).…”

Section: Introductionmentioning

confidence: 99%

The histone demethylase KDM5 is essential for larval growth inDrosophila

Secombe

Drelon

Belálcazar

2018

Preprint

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Regulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of proteins are histone H3 lysine 4 demethylases that can regulate transcription through both demethylase-dependent and independent mechanisms. While loss and overexpression of KDM5 proteins are linked to intellectual disability and cancer, respectively, their normal developmental functions remain less characterized. Drosophila melanogaster provides an ideal system to investigate KDM5 function, as it encodes a single ortholog in contrast to the four paralogs found in mammalian cells. To examine the consequences of complete loss of KDM5, we generated a null allele of Drosophila kdm5, also known as little imaginal discs (lid), and show that it is essential for development. Animals lacking KDM5 die during late pupal development but show a dramatically delayed larval development that coincides with decreased proliferation and increased cell death in imaginal discs. Interestingly, this developmental delay is independent of the well-characterized Jumonji C (JmjC) domainencoded histone demethylase activity and plant homedomain (PHD) motif-mediated chromatin binding activities of KDM5, suggesting key functions for less characterized domains. Consistent with the phenotypes observed, transcriptome analyses of kdm5 null mutant wing imaginal discs revealed the dysregulation of genes involved in several cellular processes, including cell cycle progression and DNA repair. Together, our data provide the first description of complete loss of KDM5 function in a metazoan and offer an invaluable tool for defining the biological activities of KDM5 family proteins.

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“…CPI-455 inhibits to similar extents KDM5A, B and C [18]. In agreement with a key role for KDM5 histone-demethylases in cancer progression and drug tolerance, KDM5A and KDM5B are up-regulated in many cancers, including gastric, breast and lung cancers as well as acute myeloid leukemia reviewed in [19,20].KDM5A or KDM5B up-regulation appears as a key event in the development of drug tolerance in cancer cells [18, 21] [22, 23].Replication stress (RS), referring to any hindrance to progression of the replication fork during Sphase, has been proposed to be an early step of carcinogenesis by triggering genome instability.The generation of aberrant replication fork structures containing single stranded DNA activates the RS response, primarily mediated by the kinase ATR (ATM--and Rad3--related) and its downstream effector, Chk1. This results in S--phase arrest in order to allow replication stress resolution and fork restart.…”

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confidence: 53%

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confidence: 56%

KDM5 histone-demethylases contribute to replication stress response and tolerance

Gaillard¹,

Charasson²,

Ribeyre³

et al. 2019

Preprint

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KDM5A and KDM5B histone-demethylases are overexpressed in many cancers and have been involved in drug tolerance. Here, we describe that KDM5A, together with KDM5B, contribute to replication stress (RS) response and tolerance. First, they positively regulate RRM2, the regulatory subunit of Ribonucleotide Reductase. Second, they are required for optimal activation of Chk1, a major player of the intra-S phase checkpoint that protects cells from RS. This role in Chk1 activation is probably direct since KDM5A is enriched at ongoing replication forks and associates with both PCNA and Chk1. Because RRM2 is a major determinant of replication stress tolerance, we developed cells resistant to HU, and show that KDM5A/B proteins are required for both RRM2 overexpression and tolerance to HU, in a manner that is independent of their demethylase activity. Altogether, our results indicate that KDM5A/B are major players of RS management. They also show that drugs targeting the enzymatic activity of KDM5 proteins may not affect all cancer-related consequences of KDM5A/B overexpression.KDM5 proteins belong to the JUMONJI family of histone demethylases that catalyze the demethylation of di-and tri-methylated lysines on histone and non-histone proteins. KDM5A, also known as JARID1A or RBP2 (Retinoblastoma binding protein 2), was originally discovered as a Retinoblastoma binding protein [1]. Further studies showed that KDM5A is a histone-demethylase specific to the di-and tri-methylated forms of Lys4 of Histone H3 (H3K4me2/3), a mark associated with promoters of transcriptionally active genes [2][3][4]. In agreement with its demethylase activity against an active mark of transcription, KDM5A is involved in gene repression by demethylating H3K4me3 at gene promoters. It participates in many repressive chromatin complexes, including the Polycomb complex [5], the Sin3 corepressor complex [6] and the NuRD complex [7]. KDM5A was involved in the stable repression of E2F dependent genes that occurs during terminal differentiation and senescence, two biological processes requiring permanent exit from the cell cycle [6,8]. Rb that is up-regulated during differentiation was shown to sequestrate KDM5A/Rbp2, thus impeding its repressor activity on genes required for differentiation [9]. Whereas its role in the stable repression of E2F dependent genes has been well documented, whether it is also important for the regulation of the oscillation of E2F genes transcription during the cell cycle, is less known. However, a recent report describes its interaction with p130 in order to demethylate H3K4 on E2F promoters in G0 and early G1 [10].KDM5A can also act as a transcriptional activator. When enriched in gene bodies, it plays a role in the elongation step of Polymerase II (Pol-II) by maintaining low levels of H3K4 methylation [11]. In addition, KDM5A activates genes critical for mitochondrial function and metabolism, in a manner that is independent of its demethylase activity but dependent of its C-terminal PHD3 domain that serves as docking site to H...

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JARID1 Histone Demethylases: Emerging Targets in Cancer

Cited by 85 publications

References 130 publications

Cancer stem cells and oral cancer: insights into molecular mechanisms and therapeutic approaches

Cancer stem cells and oral cancer: insights into molecular mechanisms and therapeutic approaches

The histone demethylase KDM5 is essential for larval growth inDrosophila

KDM5 histone-demethylases contribute to replication stress response and tolerance

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