Epigenetics-targeted drugs: current paradigms and future challenges

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

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Berberine inhibits the progression of breast cancer by regulating METTL3‐mediated m6A modification of FGF7 mRNA

Thoracic Cancer, Год журнала: 2024, Номер 15(17), С. 1357 - 1368

Опубликована: Май 6, 2024

Abstract Background Berberine (BBR), an isoquinoline alkaloid from Coptidis rhizoma, has been found to have powerful activities against various human malignancies, including breast cancer. However, the underlying antitumor mechanisms of BBR in cancer remain poorly understood. Methods Breast cells were cultured and treated with different doses (0, 20, 40, 60 μM) for 48 h. Cell viability, proliferation, apoptosis, invasion, migration assessed using 3‐(4, 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2H‐tetrazolium bromide (MTT), 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, wound healing assays. Fibroblast growth factor 7 (FGF7), methyltransferase‐like 3 (METTL3), insulin‐like factor‐2 mRNA‐binding protein (IGF2BP3) mRNA levels measured real‐time quantitative polymerase chain reaction (RT‐qPCR) western blot. Interaction between METTL3 FGF7 m6A was methylated RNA immunoprecipitation (MeRIP)‐qPCR (RIP) assay. Binding ability IGF2BP3 analyzed RIP Results treatment hindered cell migration, induced apoptosis. expression upregulated tissues, while its level reduced BBR‐treated tumor cells. upregulation relieved repression on malignant behaviors. In mechanism, stabilized through m6A‐IGF2BP3‐dependent mechanism naturally improved expression. inhibited vivo. Conclusion blocked metastasis partly by regulating METTL3‐mediated modification mRNA, providing a promising therapeutic target treatment.

Язык: Английский

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Electroacupuncture Serum Alleviates Ogd/R-Induced Astrocyte Damage by Regulating the AQP4 Via m6A Methylation of lncRNA MALAT1

Neurochemical Research, Год журнала: 2025, Номер 50(2)

Опубликована: Апрель 1, 2025

Язык: Английский

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Potential therapeutic targets for ischemic stroke in pre-clinical studies: Epigenetic-modifying enzymes DNMT/TET and HAT/HDAC

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Апрель 28, 2025

Ischemic stroke (IS) remains a leading cause of mortality and disability worldwide, driven by genetic predispositions environmental interactions, with epigenetics playing pivotal role in mediating these processes. Specific modifying enzymes that regulate epigenetic changes have emerged as promising targets for IS treatment. DNA methyltransferases (DNMTs), ten-eleven translocation (TET) dioxygenases, histone acetyltransferases (HATs), deacetylases (HDACs) are central to regulation. These maintain dynamic balance between methylation/demethylation acetylation/deacetylation, which critically influences gene expression neuronal survival IS. This review is based on both vivo vitro experimental studies, exploring the roles DNMT/TET HAT/HDAC IS, evaluating their potential therapeutic targets, discussing use natural compounds modulators develop novel treatment strategies.

Язык: Английский

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Circ_0008146 Exacerbates Ferroptosis via Regulating the miR-342-5p/ACSL4 Axis After Cerebral Ischemic/Reperfusion

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 4957 - 4973

Опубликована: Июль 1, 2024

Purpose: Acute ischemic stroke (AIS) has seriously threatened people's health worldwide and there is an urge need for early diagnosis effective treatment of AIS. This research intended to clarify the regulatory role circ_0008146/miR-342-5p/ACSL4 axis in Methods: High-throughput small RNA sequencing analysis was adapted identify differentially expressed miRNAs between AIS control group. The circ_0008146, miR-342-5p, ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models constructed C57BL/6J mice. Assay kits used determine Fe 2+ a battery oxidative stress lipid peroxidation indicators, including ROS, MDA, LPO, SOD GSH/GSSG ratio. protein measured Western blot. behavioral function assessed using neurobehavioral tests. TTC staining employed visualize infarction size. Nissl detect histopathological changes. Receiver operating characteristic curve correlation applied investigate clinical value association miR-342-5p ACSL4. Results: A total 44 patients 49 healthy controls enrolled our study. unveiled significant decrease patients. MiR-342-5p inhibited RSL3-induced ferroptosis after ischemic/reperfusion injury vivo targeting ferroptosis-related gene Circ_0008146 acted as sponge overexpression circ_0008146 increased neurological deficits brain contributed via sponging regulate Plasma demonstrated good diagnostic Conclusion: study provides first evidence show that exacerbates neuronal miR-342-5p/ACSL4 axis. Furthermore, holds promise viable therapeutic target practical biomarkers Keywords: stroke, miRNA, circRNA, ferroptosis, biomarker

Язык: Английский

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Methyltransferase METTL3 regulates neuropathic pain through m6A methylation modification of SOCS1

Neuropharmacology, Год журнала: 2024, Номер 261, С. 110176 - 110176

Опубликована: Сен. 30, 2024

Язык: Английский

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M1 Microglia-Derived Exosomes Promote A1 Astrocyte Activation and Aggravate Ischemic Injury via circSTRN3/miR-331-5p/MAVS/NF-κB Pathway

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 9285 - 9305

Опубликована: Ноя. 1, 2024

After ischemic stroke (IS), microglia and astrocytes undergo polarization, transforming into a pro-inflammatory phenotype (M1 or A1). According to previous studies, exosomes might play an important role in the interplay between M1 A1 after IS.

Язык: Английский

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METTL14 Promotes Ischemic Stroke-induced Brain Injury by Stabilizing HDAC3 Expression in an m6A-IGF2BP3 Mechanism

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер unknown

Опубликована: Окт. 25, 2024

Язык: Английский

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ROS-responsive quercetin-based polydopamine nanoparticles for targeting ischemic stroke by attenuating oxidative stress and neuroinflammation

International Journal of Pharmaceutics, Год журнала: 2024, Номер 669, С. 125087 - 125087

Опубликована: Дек. 14, 2024

Язык: Английский

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