Histone Lysine Methylation Modification and Its Role in Vascular Calcification

Cao, Ye-Chi; Shan, Su-Kang; Guo, Bei; Li, Changchun; Li, Fuxingzi; Zheng, Minghui; Xu, Qiu-Shuang; Wang, Yi; Lei, Li-Min; Tang, Ke-Xin; Ou-Yang, Wen-Lu; Duan, Jia-Yue; Wu, Yun-Yun; Ullah, Muhammad Hasnain Ehsan; Zhou, Zhi-Ang; Xing, Feng; Lin, Xiao; Wu, Feng; Liao, Xiao‐Bo; Yuan, Ling‐Qing

doi:10.3389/fendo.2022.863708

Cited by 12 publications

(10 citation statements)

References 192 publications

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“…Methylation of H3K4, H3K26, H3K36, H3K79, and H4K12 is mainly involved in gene activation, while methylation of H3K9, H3K27, H3K56, H4K5, and H4K20 is related to gene silencing. 157 Highly expressed in tumors, SUV39H1, SETDB2 and G9a mainly target H3K9 for methylation, and H3K4 is the methylated target of KMT2A-E and KMT7. KMT3A-G can methylate H3K36 and is overexpressed in multiple cancers.…”

Section: Histone Deacetylases (Hdacs)mentioning

confidence: 99%

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Targeting epigenetic regulators to overcome drug resistance in cancers

Wang

2023

Sig Transduct Target Ther

119

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Drug resistance is mainly responsible for cancer recurrence and poor prognosis. Epigenetic regulation is a heritable change in gene expressions independent of nucleotide sequence changes. As the common epigenetic regulation mechanisms, DNA methylation, histone modification, and non-coding RNA regulation have been well studied. Increasing evidence has shown that aberrant epigenetic regulations contribute to tumor resistance. Therefore, targeting epigenetic regulators represents an effective strategy to reverse drug resistance. In this review, we mainly summarize the roles of epigenetic regulation in tumor resistance. In addition, as the essential factors for epigenetic modifications, histone demethylases mediate the histone or genomic DNA modifications. Herein, we comprehensively describe the functions of the histone demethylase family including the lysine-specific demethylase family, the Jumonji C-domain-containing demethylase family, and the histone arginine demethylase family, and fully discuss their regulatory mechanisms related to cancer drug resistance. In addition, therapeutic strategies, including small-molecule inhibitors and small interfering RNA targeting histone demethylases to overcome drug resistance, are also described.

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Section: Histone Deacetylases (Hdacs)mentioning

confidence: 99%

“…Notably, much attention has been paid to the fact that EZH2 is mainly involved in tumorigenesis by regulating histone H3 lysine 27 (H3K27) methylation, whose overexpression is associated with poor prognosis. [157][158][159][160] Histone methyltransferases are closely related to drug resistance (Fig. 3).…”

Section: Histone Deacetylases (Hdacs)mentioning

confidence: 99%

Targeting epigenetic regulators to overcome drug resistance in cancers

Wang

2023

Sig Transduct Target Ther

119

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“…Recently, SMYD2 and SMYD3, together with other SET proteins, have been shown to function in the development of vascular disease. The methylation of H3K4 and H3K36 was dependent on SET and associated with vascular calcification [ 104 , 105 ]. To evaluate the pathophysiology of vascular calcification, the development of pharmacologic agents that target and reverse the methylation of lysine groups on histones to restore homeostasis has been proposed.…”

Section: Smyd-proteins Structure Function and Medicinal Potentialmentioning

confidence: 99%

Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases

et al. 2023

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A comprehensive understanding of the mechanisms involved in epigenetic changes in gene expression is essential to the clinical management of diseases linked to the SMYD family of lysine methyltransferases. The five known SMYD enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine (SAM) to specific lysines on histones and non-histone substrates. SMYDs family members have distinct tissue distributions and tissue-specific functions, including regulation of development, cell differentiation, and embryogenesis. Diseases associated with SMYDs include the repressed transcription of SMYD1 genes needed for the formation of ion channels in the heart leading to heart failure, SMYD2 overexpression in esophageal squamous cell carcinoma (ESCC) or p53-related cancers, and poor prognosis associated with SMYD3 overexpression in more than 14 types of cancer including breast cancer, colon cancer, prostate cancer, lung cancer, and pancreatic cancer. Given the importance of epigenetics in various pathologies, the development of epigenetic inhibitors has attracted considerable attention from the pharmaceutical industry. The pharmacologic development of the inhibitors involves the identification of molecules regulating both functional SMYD SET (Suppressor of variegation, Enhancer of Zeste, Trithorax) and MYND (Myeloid-Nervy-DEAF1) domains, a process facilitated by available X-ray structures for SMYD1, SMYD2, and SMYD3. Important leads for potential pharmaceutical agents have been reported for SMYD2 and SMYD3 enzymes, and six epigenetic inhibitors have been developed for drugs used to treat myelodysplastic syndrome (Vidaza, Dacogen), cutaneous T-cell lymphoma (Zoinza, Isrodax), and peripheral T-cell lymphoma (Beleodag, Epidaza). The recently demonstrated reversal of SMYD histone methylation suggests that reversing the epigenetic effects of SMYDs in cancerous tissues may be a desirable target for pharmacological development.

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“…Nevertheless, some researchers have proposed the idea that methylation of histone H3 at lysine 9 (H3K9) corresponds to gene inactivation and precedes DNA methylation (39). Histone methylation is a PTM change mediated by histone methyltransferase, which has been confirmed to be related to the occurrence and development of a variety of diseases, such as cardiovascular and cerebrovascular diseases, cancer, aging, and reproductive system diseases (40)(41)(42). Recently, histone methylation has been involved in the pathogenesis of PCOS.…”

Section: Methylationmentioning

confidence: 99%

Posttranslational modifications in pathogenesis of PCOS

et al. 2022

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Polycystic ovary syndrome (PCOS) is a lifelong reproductive, metabolic, and psychiatric disorder that affects 5-18% of women, which is associated with a significantly increased lifetime risk of concomitant diseases, including type 2 diabetes, psychiatric disorders, and gynecological cancers. Posttranslational modifications (PTMs) play an important role in changes in protein function and are necessary to maintain cellular viability and biological processes, thus their maladjustment can lead to disease. Growing evidence suggests the association between PCOS and posttranslational modifications. This article mainly reviews the research status of phosphorylation, methylation, acetylation, and ubiquitination, as well as their roles and molecular mechanisms in the development of PCOS. In addition, we briefly summarize research and clinical trials of PCOS therapy to advance our understanding of agents that can be used to target phosphorylated, methylated, acetylated, and ubiquitinated PTM types. It provides not only ideas for future research on the mechanism of PCOS but also ideas for PCOS treatments with therapeutic potential.

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Histone Lysine Methylation Modification and Its Role in Vascular Calcification

Cited by 12 publications

References 192 publications

Targeting epigenetic regulators to overcome drug resistance in cancers

Targeting epigenetic regulators to overcome drug resistance in cancers

Targeting Epigenetic Changes Mediated by Members of the SMYD Family of Lysine Methyltransferases

Posttranslational modifications in pathogenesis of PCOS

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