A Review on Molecular Docking on HDAC Isoforms: Novel Tool for Designing Selective Inhibitors DOI Creative Commons
Aliki Drakontaeidi, Eleni Pontiki

Pharmaceuticals, Год журнала: 2023, Номер 16(12), С. 1639 - 1639

Опубликована: Ноя. 22, 2023

Research into histone deacetylases (HDACs) has experienced a remarkable surge in recent years. These enzymes are key regulators of several fundamental biological processes, often associated with severe and potentially fatal diseases. Inhibition their activity represents promising therapeutic approach prospective strategy for the development new agents. A critical aspect inhibition is to achieve selectivity terms enzyme isoforms, which essential improve treatment efficacy while reducing undesirable pleiotropic effects. The computational chemistry tools, particularly molecular docking, greatly enhancing precision designing molecules inherent potential specific activity. Therefore, it was considered necessary review docking studies conducted on major isozymes order identify interactions each selective HDAC inhibitor. In particular, most (1, 2, 3, 6, 8) have been thoroughly investigated within scope this review.

Язык: Английский

Epigenetics-targeted drugs: current paradigms and future challenges DOI Creative Commons

Wanlin Dai,

Xinbo Qiao, Yuanyuan Fang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Язык: Английский

Процитировано

34
Histone deacetylase-mediated tumor microenvironment characteristics and synergistic immunotherapy in gastric cancer DOI Creative Commons
Yilin Lin, Xiangxiang Jing, Zhihua Chen

и другие.

Theranostics, Год журнала: 2023, Номер 13(13), С. 4574 - 4600

Опубликована: Янв. 1, 2023

Background: Studies have shown that the expression of histone deacetylases (HDACs) is significantly related to tumor microenvironment (TME) in gastric cancer. However, a single molecule or several molecules does not accurately reflect TME characteristics guide immunotherapy Methods: We constructed an HDAC score (HDS) based on level HDACs. The single-cell transcriptome was used analyze underlying factors contributing differences immune infiltration between patients with high and low HDS. In vitro vivo experiments validated strategy transforming cold tumors into hot immunotherapy. Results: According HDACs, we HDS model characterize TME. found had stronger immunogenicity could benefit more from than those score. AUC value combined positive (CPS)for predicting efficacy as 0.96. By paired bulk sequencing analysis, levels CD4+ T cells, CD8+ cells NK were decreased group, which may be induced by MYH11+ fibroblasts, CD234+ endothelial CCL17+ pDCs via MIF signaling pathway. Inhibition pathway confirmed potentially enhance infiltration. addition, our analysis revealed GPX4 inhibitors might effective for knockout inhibited PD-L1 promoted activation cells. Conclusion: This evaluate predict efficacy. important synergistic

Язык: Английский

Процитировано

30
Single-nucleus multiomics reveals the gene regulatory networks underlying sex determination of murine primordial germ cells DOI Creative Commons
Adriana K. Alexander, Karina F. Rodriguez, Yuying Chen

и другие.

eLife, Год журнала: 2025, Номер 13

Опубликована: Март 10, 2025

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial (PGCs) are the bipotential precursors mature gametes that commit to an oogenic or spermatogenic fate in response sex-determining cues from fetal gonad. The processes required PGCs integrate respond signals somatic environment gonads not well understood. In this study, we developed first single-nucleus multiomics map chromatin accessibility gene expression murine PGC both XX XY embryos. Profiling cell-type-specific transcriptomes regions open same cell captured molecular signatures networks underlying sex determination. Joint RNA ATAC data single resolved previously unreported subpopulations cataloged a multimodal reference atlas differentiating clusters. We discovered regulatory element precedes development, suggesting changes may prime lineage commitment prior differentiation. Similarly, found dimorphism increased temporally PGCs. Combining sequencing data, computationally mapped cohort transcription factors regulate sexually dimorphic genes For example, enriched factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, ZFX. Sex-specific enrichment forkhead-box POU6 families was also observed Finally, determined temporal patterns WNT, BMP, RA signaling determination, our discovery analyses identified potentially new communication pathways between supporting Our results illustrate diversity involved programming toward sex-specific fate.

Язык: Английский

Процитировано

1
The role of protein acetylation in carcinogenesis and targeted drug discovery DOI Creative Commons
Jingru Yang, Cong Song, Xianquan Zhan

и другие.

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Сен. 12, 2022

Protein acetylation is a reversible post-translational modification, and involved in many biological processes cells, such as transcriptional regulation, DNA damage repair, energy metabolism, which an important molecular event associated with wide range of diseases cancers. dynamically regulated by histone acetyltransferases (HATs) deacetylases (HDACs) homeostasis. The abnormal level might lead to the occurrence deterioration cancer, closely related various pathophysiological characteristics malignant phenotypes, promotes cancer cells adapt tumor microenvironment. Therapeutic modalities targeting protein are potential therapeutic strategy. This article discussed roles pathology drugs acetylation, offers contributions clarification carcinogenesis, discovery for cancers, lays foundation precision medicine oncology.

Язык: Английский

Процитировано

29
MicroRNA-383: A tumor suppressor miRNA in human cancer DOI Creative Commons
Abdollah Jafarzadeh,

Majid Noori,

Shaghayegh Sarrafzadeh

и другие.

Frontiers in Cell and Developmental Biology, Год журнала: 2022, Номер 10

Опубликована: Окт. 13, 2022

Downregulated expression of anti-tumor miR-383 has been found in many kinds cancer. MiR-383 family members can directly target the 3′-untranslated region (3′-UTR) mRNA some pro-tumor genes to attenuate several cancer-related processes, including cell proliferation, invasion, migration, angiogenesis, immunosuppression, epithelial-mesenchymal transition, glycolysis, chemoresistance, and development cancer stem cells, whilst promoting apoptosis. Functionally, operates as a tumor inhibitor miRNA types cancer, breast hepatocellular carcinoma, gastric pancreatic colorectal esophageal lung head neck glioma, medulloblastoma, melanoma, prostate cervical oral squamous thyroid B-cell lymphoma. Both effects have attributed ovarian However, only were reported cholangiocarcinoma. The restoration could be considered possible treatment for This review discusses human cancers, emphasizing their downstream potential approaches.

Язык: Английский

Процитировано

26
Oxidized low-density lipoprotein regulates macrophage polarization in atherosclerosis DOI

Yonghang He,

Tingting Liu

International Immunopharmacology, Год журнала: 2023, Номер 120, С. 110338 - 110338

Опубликована: Май 19, 2023

Язык: Английский

Процитировано

16
MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications DOI Creative Commons
Joanna Szczepanek, Andrzej Tretyn

Biomolecules, Год журнала: 2023, Номер 13(11), С. 1590 - 1590

Опубликована: Окт. 28, 2023

In the past decade, significant advances in molecular research have provided a deeper understanding of intricate regulatory mechanisms involved carcinogenesis. MicroRNAs, short non-coding RNA sequences, exert substantial influence on gene expression by repressing translation or inducing mRNA degradation. context cancer, miRNA dysregulation is prevalent and closely associated with various stages carcinogenesis, including initiation, progression, metastasis. One crucial aspect cancer phenotype activity histone-modifying enzymes that govern chromatin accessibility for transcription factors, thus impacting expression. Recent studies revealed miRNAs play role modulating these enzymes, leading to implications genes related proliferation, differentiation, apoptosis cells. This article provides an overview current which regulate cancer. Both direct indirect through enzyme are discussed. Additionally, potential therapeutic arising from manipulation selectively impact presented. The insights this analysis hold promise, suggesting utility as tools precise regulation chromatin-related processes A contemporary focus opens pathways can effectively control tumor cell growth dissemination.

Язык: Английский

Процитировано

14
The role of histone acetylation in transcriptional regulation and seed development DOI Open Access
Yan Chen, Peiguo Guo, Zhicheng Dong

и другие.

PLANT PHYSIOLOGY, Год журнала: 2023, Номер 194(4), С. 1962 - 1979

Опубликована: Ноя. 18, 2023

Abstract Histone acetylation is highly conserved across eukaryotes and has been linked to gene activation since its discovery nearly 60 years ago. Over the past decades, histone evidenced play crucial roles in plant development response various environmental cues. Emerging data indicate that one of defining features “open chromatin,” while role transcription remains controversial. In this review, we briefly describe acetylation, mechanism regulating yeast mammals, summarize research progress acetylation. Furthermore, also emphasize effect on seed potential use breeding. A comprehensive knowledge might provide new more flexible perspectives enhance crop yield stress resistance.

Язык: Английский

Процитировано

12
Folding of Class IIa HDAC Derived Peptides into α-helices Upon Binding to Myocyte Enhancer Factor-2 in Complex with DNA DOI
Monica Chinellato, Stefano Perin,

Alberto Carli

и другие.

Journal of Molecular Biology, Год журнала: 2024, Номер 436(9), С. 168541 - 168541

Опубликована: Март 16, 2024

Язык: Английский

Процитировано

3
Single-nucleus multiomics reveals the gene-regulatory networks underlying sex determination of murine primordial germ cells DOI Open Access
Adriana K. Alexander, Karina F. Rodriguez, Yuying Chen

и другие.

Опубликована: Май 21, 2024

Accurate specification of female and male germ cells during embryonic development is critical for sexual reproduction. Primordial (PGCs) are the bipotential precursors mature gametes that commit to an oogenic or spermatogenic fate in response sex-determining cues from fetal gonad. The processes required PGCs integrate respond signals somatic environment gonads not understood. In this study, we developed first single-nucleus multiomics map chromatin accessibility gene expression murine PGC both XX XY embryos. Profiling cell-type specific transcriptomes regions open same cell captured molecular signatures networks underlying sex determination. Joint RNA ATAC data single resolved previously unreported subpopulations cataloged a multimodal reference atlas differentiating clusters. We discovered regulatory element precedes development, suggesting changes may prime lineage commitment prior differentiation. Similarly, found dimorphism increased temporally PGCs. Combining sequencing data, computationally mapped cohort transcription factors regulate sexually dimorphic genes For example, enriched factors, TFAP2c, TCFL5, GATA2, MGA, NR6A1, TBX4, ZFX. Sex-specific enrichment forkhead-box POU6 families was also observed Finally, determined temporal patterns WNT, BMP, RA signaling determination, our discovery analyses identified potentially new communication pathways between supporting Our results illustrate diversity involved programming towards sex-specific fate.

Язык: Английский

Процитировано

3