Endothelial KDM5B Regulated by Piezo1 Contributes to Disturbed Flow Induced Atherosclerotic Plaque Formation DOI Creative Commons
Lili Wu, Shanshan Jiang,

Xiao Zhou

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

ABSTRACT Epigenetic modifications play an important role in disturbed flow (d‐flow) induced atherosclerotic plaque formation. By analysing a scRNA‐seq dataset of the left carotid artery (LCA) under d‐flow conditions, we found that Jarid1b (KDM5B) was upregulated primarily subcluster endothelial cells response to stimulation. We therefore investigated mechanism KDM5B expression and cell. Intriguingly, activation Piezo1, major mechanosensor, promote expression, which reversed by Piezo1 inhibition HUVECs. Downstream ETS1 c‐JUN phosphorylation were enhanced or activation, leading increase expression. Furthermore, knockdown either prevent H3K4me3 demethylation, supported pharmacological RNA sequencing on sh Kdm5b HUVECs implied is associated with inflammation atherosclerosis. Using partial ligation surgery f/f Cdh5 cre mice mAAV ‐ PCSK9 D377Y infected, showed deficiency reduced lesions hypercholesterolemic mice. Our findings indicate via pathway promotes formation, providing targets for prevention therapeutic intervention

Language: Английский

Editorial: The emerging role of protein methylation/demethylation modification in disease and homeostasis DOI Creative Commons
Y. Liu, Jianfei Lu, Xin Peng

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 10, 2025

The significance of protein methylation and demethylation extends beyond basic cellular functions; they are critical in numerous biological processes, including development, differentiation, epigenetic regulation. For instance, histone is a well-studied modification that orchestrates chromatin structure gene expression, influencing identity function. Additionally, the non-histone proteins, such as transcription factors signaling molecules, further underscores complexity importance these modifications regulating activities. These not only fundamental to functions but also have profound implications more complex phenomena diseases. Understanding intricate mechanisms underlying crucial for unraveling their roles normal physiology disease pathology. As research this area progresses, it holds promise revealing potential therapeutic opportunities could transform our approach treating various proteins target, involvement chemoresistance, along with inhibitors 104 action. review addresses current challenges future directions PMT 105 combating cancer chemoresistance.

Language: Английский

Citations

0
Histone demethylase inhibitor KDM5-C70 regulates metabolomic and lipidomic programming during an astrocyte differentiation of rat neural stem cell DOI Creative Commons

Minki Shim,

Thin Thin San,

Bohyun Shin

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 13, 2025

Abstract Lysine-specific histone demethylase (KDM) 5 inhibition by KDM5-C70 induces astrocytogenesis and highlights the importance of modulation methylation in cell fate specification. This study investigated role inhibitor modulating metabolic lipidomic landscape during astrocyte differentiation rat neural stem cells (NSCs). Using chemical derivatisation combined with gas chromatography-mass spectrometry, 42 metabolites were detected, indicating potential regulation phospholipid metabolism. Subsequent analysis, employing reverse-phase liquid chromatography high-resolution quadrupole time-of-flight mass identified 180 lipid species 9 subclasses. Integrative analysis revealed that promoted through epigenetic changes linked to attenuation phosphatidylethanolamine (PE) biosynthesis pathways. The reduced expression transcripts related PE highlighted significance pathway influencing decisions. These quantitative metabolomic analyses not only advance our understanding NSC but also lay groundwork for therapeutic strategies targeting pathways neurodegenerative diseases injuries.

Language: Английский

Citations

0
Abacavir enhances the efficacy of Doxorubicin via inhibition of histone demethylase KDM5B in breast cancer DOI

Anmi Jose,

Pallavi Kulkarni, Naveena A. N. Kumar

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 3, 2025

Abstract KDM5B, a lysine-specific histone demethylase, is widely upregulated in breast cancer. The current study investigated the role of KDM5B cancer and explored repurposing potential antiviral drug abacavir (ABC). cytotoxic effects effect ABC sensitization on doxorubicin (DOX) efficacy were evaluated using 2-D 3-D cell culture models. expression was elevated tissues compared to normal tissues. In vitro studies demonstrated that treatment reduced cells increased their sensitivity towards DOX. induced late apoptosis S phase arrest, while + DOX combination led S/G2 apoptosis, death. Data generated from patient-derived tumoroids corroborated culture-based findings. Additionally, molecular docking indicated active metabolite carbovir triphosphate (CBV-TP) could interact with DNA polymerase β-DNA complex, suggesting its mechanism be incorporated into synthesis cycle, leading cycle arrest tumor cells. Our findings highlight target This approach enhanced DOX, which allow further dose reduction side effects, offering promising therapeutic strategy.

Language: Английский

Citations

0
The Role of Medicinal Plants in Modulating Epigenetic Mechanisms: Implications for Cancer Prevention and Therapy DOI

Khadra Afaf Bendrihem,

Aicha Mouane,

Manel Azzi

et al.

Phytotherapy Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Cancer remains a significant global health challenge, with its progression driven by both genetic mutations and reversible epigenetic modifications. This review highlights the potential of phytochemicals to modulate mechanisms for cancer prevention treatment. Natural compounds such as quercetin, EGCG, genistein, β-elemene interact key processes DNA methylation, histone modifications, non-coding RNA regulation. These enable reactivation tumor suppressor genes, increased sensitivity conventional therapy mitigation drug resistance. For instance, EGCG improves efficacy cisplatin altering methylation patterns, while genistein influences breast through HER2 pathway However, challenges low bioavailability, variability in compound composition, need robust clinical validation remain. Further high-quality trials are required confirm safety these therapy.

Language: Английский

Citations

0
Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer DOI Creative Commons

Ru-Yi Chen,

Lijian Ding, Yanjun Liu

et al.

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(10), P. 459 - 459

Published: Oct. 5, 2024

Triple-negative breast cancer (TNBC) is a subtype of with high mortality and drug resistance no targeted available at present. Compound

Language: Английский

Citations

2
PRMT7 in cancer: Structure, effects, and therapeutic potentials DOI
Guan‐Jun Yang, Yanjun Liu,

Ru-Yi Chen

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117103 - 117103

Published: Nov. 26, 2024

Language: Английский

Citations

2
Advancements in Clinical Research and Emerging Therapies for Triple-Negative Breast Cancer Treatment DOI
Lili Xu, Pengtao Xu, Jingsong Wang

et al.

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: unknown, P. 177202 - 177202

Published: Dec. 1, 2024

Language: Английский

Citations

1
Structure-Based identification of a potent KDM7A inhibitor exerts anticancer activity through transcriptionally reducing MKRN1 in taxol- resistant and -sensitive triple-negative breast cancer cells DOI
Jinjin Shi, Yanjun Liu, Zhiguo Liu

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 153, P. 107945 - 107945

Published: Nov. 5, 2024

Language: Английский

Citations

0
Endothelial KDM5B Regulated by Piezo1 Contributes to Disturbed Flow Induced Atherosclerotic Plaque Formation DOI Creative Commons
Lili Wu, Shanshan Jiang,

Xiao Zhou

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(23)

Published: Dec. 1, 2024

ABSTRACT Epigenetic modifications play an important role in disturbed flow (d‐flow) induced atherosclerotic plaque formation. By analysing a scRNA‐seq dataset of the left carotid artery (LCA) under d‐flow conditions, we found that Jarid1b (KDM5B) was upregulated primarily subcluster endothelial cells response to stimulation. We therefore investigated mechanism KDM5B expression and cell. Intriguingly, activation Piezo1, major mechanosensor, promote expression, which reversed by Piezo1 inhibition HUVECs. Downstream ETS1 c‐JUN phosphorylation were enhanced or activation, leading increase expression. Furthermore, knockdown either prevent H3K4me3 demethylation, supported pharmacological RNA sequencing on sh Kdm5b HUVECs implied is associated with inflammation atherosclerosis. Using partial ligation surgery f/f Cdh5 cre mice mAAV ‐ PCSK9 D377Y infected, showed deficiency reduced lesions hypercholesterolemic mice. Our findings indicate via pathway promotes formation, providing targets for prevention therapeutic intervention

Language: Английский

Citations

0