Mechanistic Insights into the Anti-Hepatocellular Carcinoma Effects of ACY-1215: p53 Acetylation and Ubiquitination Regulation DOI Creative Commons

Yi Yin,

Yu-Tong Du, Yiting Xu

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 338 - 338

Published: May 8, 2025

As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, selective Histone deacetylase 6 (HDAC6) inhibitor, and mechanism targeting p53 regulation. In vitro studies conducted with HepG2 SMMC-7721 cells revealed that ACY-1215 markedly inhibited HCC cell proliferation, migratory capacity, invasive potential, as evidenced by CCK-8, colony formation, Transwell assays. Furthermore, induced caspase-dependent apoptosis. Mechanistically, enhanced acetylation disrupting HDAC6-p53 interaction, thereby stabilizing protein levels. Concurrently, it Murine Double Minute 2 (MDM2)-mediated ubiquitination, blocking proteasomal degradation prolonging half-life. dual modulation restored transcriptional activity, leading to upregulation downstream effector molecules associated cycle regulation Collectively, our findings reveal exerts potent effects through coordinated offering novel dual-targeting strategy for therapy.

Language: Английский

PANoptosis-related genes in the prognosis and immune landscape of hepatocellular carcinoma DOI Creative Commons
Xiaowu Wang,

Liangchen Qu,

Zhikai Wen

et al.

Immunologic Research, Journal Year: 2025, Volume and Issue: 73(1)

Published: Feb. 13, 2025

Language: Английский

Citations

0
Comprehensive system biology analysis of microRNA-101-3p regulatory network identifies crucial genes and pathways in hepatocellular carcinoma DOI Creative Commons

Nasim Rahimi‐Farsi,

Abozar Ghorbani, Negar Mottaghi-Dastjerdi

et al.

Journal of Genetic Engineering and Biotechnology, Journal Year: 2025, Volume and Issue: 23(1), P. 100471 - 100471

Published: Feb. 18, 2025

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. This study aimed to explore the role hsa-miR-101-3p in HCC pathogenesis by identifying key genes and pathways. A comprehensive bioinformatics analysis revealed twelve hub (ETNK1, BICRA, IL1R1, KDM3A, ARID2, GSK3β, EZH2, NOTCH1, SMARCA4, FOS, CREB1, CASP3) highlighted their involvement crucial oncogenic pathways, including PI3K/Akt, mTOR, MAPK, TGF-β. Gene expression showed significant overexpression ETNK1, CASP3 tissues, correlating with poorer survival outcomes. Drug screening identified therapeutic candidates, Tazemetostat for EZH2 lithium compounds underscoring potential targeted treatment. These findings provide novel insights into complexity pathogenesis, suggesting that could serve as diagnostic or prognostic biomarkers targets. While bioinformatics-driven, this offers strong basis future clinical validation advance precision medicine HCC.

Language: Английский

Citations

0
HCC and Immunotherapy: The Potential Predictive Role of Gut Microbiota and Future Therapeutic Strategies DOI Creative Commons
Carmelo Laface, E Lauricella, Girolamo Ranieri

et al.

Onco, Journal Year: 2025, Volume and Issue: 5(1), P. 9 - 9

Published: Feb. 27, 2025

During the last decade, a new therapeutic revolution has involved management of hepatocellular carcinoma (HCC). This is made possible thanks to documented efficacy immunotherapy for this disease. In addition, evidence demonstrated role gut–liver axis and gut microbiota in host homeostasis, tumor development, response therapies. particular, intestinal dysbiosis can alter microenvironment, leading activation intracellular signaling pathways that promote carcinogenesis. The composition proved influence immune checkpoint inhibitors (ICIs) drug toxicities. Therefore, review aims deepen knowledge about immunomodulatory its employment as diagnostic predictive biomarkers diagnosis HCC immunotherapy, respectively. research was conducted through analysis Pubmed Web Science (WoS) databases literature studies on relationship between from 2015 2025.

Language: Английский

Citations

0
Mechanistic Insights into the Anti-Hepatocellular Carcinoma Effects of ACY-1215: p53 Acetylation and Ubiquitination Regulation DOI Creative Commons

Yi Yin,

Yu-Tong Du, Yiting Xu

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(5), P. 338 - 338

Published: May 8, 2025

As a major global health challenge, hepatocellular carcinoma (HCC) still faces substantial limitations in its treatment options. This study investigates the anti-HCC potential of ACY-1215, selective Histone deacetylase 6 (HDAC6) inhibitor, and mechanism targeting p53 regulation. In vitro studies conducted with HepG2 SMMC-7721 cells revealed that ACY-1215 markedly inhibited HCC cell proliferation, migratory capacity, invasive potential, as evidenced by CCK-8, colony formation, Transwell assays. Furthermore, induced caspase-dependent apoptosis. Mechanistically, enhanced acetylation disrupting HDAC6-p53 interaction, thereby stabilizing protein levels. Concurrently, it Murine Double Minute 2 (MDM2)-mediated ubiquitination, blocking proteasomal degradation prolonging half-life. dual modulation restored transcriptional activity, leading to upregulation downstream effector molecules associated cycle regulation Collectively, our findings reveal exerts potent effects through coordinated offering novel dual-targeting strategy for therapy.

Language: Английский

Citations

0