4.4 Review

Differential molecular mechanistic behavior of HDACs in cancer progression

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Summary: This study found that Honokiol can prevent the metastatic dissemination of gastric cancer cells by inhibiting HDAC3 activity/expression. The results suggest that Honokiol inhibits HDAC3 activity by suppressing the activation of the NF-Bp65/CEBPβ signaling pathway, thereby inhibiting the migration and invasion of cancer cells. In addition, Honokiol increases the expression of ER stress markers, inhibits the expression of EMT-associated epithelial markers, and decreases Wnt/β-catenin activity, thereby blocking the metastasis of gastric cancer.

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Summary: The mortality of patients with pancreatic ductal adenocarcinoma (PDAC) is strongly associated with metastasis, and transcriptional and epigenetic rewiring can contribute to the metastatic process. This study shows that HDAC2 plays a crucial role in undifferentiated PDAC by controlling cell cycle and metastasis. HDAC2 maintains the metastatic program by controlling the expression of several prosurvival receptor tyrosine kinases connected to mesenchymal PDAC, and impairs the tumor-suppressive arm of the TGFI3 pathway.

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Devaraj Ezhilarasan et al.

Summary: Sirtuins, particularly SIRT1, SIRT2, and SIRT3, play various roles in oral cancer. SIRT1 is reported to act as a tumor suppressor, while SIRT2's role remains unclear in oral cancer. SIRT3 expression is positively correlated with oral malignancies.

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Summary: This study systematically reviewed the literature on the hematological consequences of Valproate (VPA) therapy in pediatric patients. The results showed that even at therapeutic doses, VPA could cause severe hematotoxicity in children. The most common complications associated with VPA therapy were neutropenia, thrombocytopenia, and bone marrow depression. However, after discontinuation of VPA and starting other antiepileptic drugs or reducing the VPA dose, all hematological damages were resolved and improvements in hematological parameters were observed within two weeks.

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Linchong Sun et al.

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Jessica L. S. Zylla et al.

Summary: We investigated the potential use of the small molecule epigenetic modulator 4SC-202 as a therapeutic or adjuvant for Triple Negative Breast Cancer (TNBC). The study showed that 4SC-202 effectively killed tumor cells, reduced their ability to migrate, and decreased metastasis and tumor burden in a murine model of TNBC. This preclinical study provides critical information on the potential efficacy of 4SC-202 for TNBC.

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Class I and II Histone Deacetylase Inhibitor LBH589 Promotes Endocrine Differentiation in Bone Marrow Derived Human Mesenchymal Stem Cells and Suppresses Uncontrolled Proliferation

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Summary: Mesenchymal stem cells are valuable in treating degenerative and autoimmune diseases, but they pose a risk of tumor formation. Histone deacetylase inhibitors can regulate differentiation and proliferation of stem cells, contributing to potential in cell therapy advancements.

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Non-histone substrates of histone deacetylases as potential therapeutic targets in epilepsy

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Summary: The review explores the role of HDACs in epilepsy, focusing on their action on non-histone substrates and the potential of HDACi as anti-epileptic drugs. It also discusses the importance of identifying novel targets of HDACs for more effective anti-epileptogenic therapy.

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Oncogenic miRNA-1908 targets HDAC10 and promotes the aggressive phenotype of cervical cancer cell

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Summary: MicroRNA miR-1908 is significantly upregulated in cervical cancer, promoting cell growth and invasion, while downregulation has the opposite effect. It targets and regulates the expression of histone deacetylase 10 (HDAC10), influencing aggressive phenotypes of cervical cancer cells.

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HDAC6 as privileged target in drug discovery: A perspective

Sravani Pulya et al.

Summary: HDAC6, a class IIB HDAC isoenzyme, plays a unique role in regulating various disease states through targeting non-histone proteins. While several HDAC6 inhibitors have been developed, more work is needed to identify highly selective and potent inhibitors. Targeting HDAC6 has been found to be effective for therapeutic purposes in different disease conditions.

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METTL14-regulated PI3K/Akt signaling pathway via PTEN affects HDAC5-mediated epithelial-mesenchymal transition of renal tubular cells in diabetic kidney disease

Zhaoxia Xu et al.

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HDAC11 Regulates Glycolysis through the LKB1/AMPK Signaling Pathway to Maintain Hepatocellular Carcinoma Stemness

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Summary: The study reveals that HDAC11 is highly expressed in HCC and its loss can reduce hepatocellular tumorigenesis and prolong survival. Loss of HDAC11 promotes histone acetylation in the promoter of LKB1 gene, activating the AMPK signaling pathway to inhibit glycolysis and suppress cancer stemness and HCC progression.

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Histone deacetylase 6 acts upstream of DNA damage response activation to support the survival of glioblastoma cells

Wen-Bin Yang et al.

Summary: This study illustrates the relationship between DDR gene expression and treatment resistance in GBM, highlighting the potential therapeutic role of the HDAC6 inhibitor MPT0B291 in GBM cells. MPT0B291 effectively reduces the expression of DNA damage repair genes, enhances cytotoxicity in GBM cells, and extends survival in mouse models.

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Afua Adjeiwaa Mensah et al.

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The Emerging Role of Epigenetics in Therapeutic Targeting of Cardiomyopathies

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Nonredundant, isoform-specific roles of HDAC1 in glioma stem cells

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Ji-Eun Lee et al.

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Deacetylation of Miro1 by HDAC6 blocks mitochondrial transport and mediates axon growth inhibition

Ashley L. Kalinski et al.

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HDAC9 overexpression confers invasive and angiogenic potential to triple negative breast cancer cells via modulating microRNA-206

Eric Salgado et al.

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Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation

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Jacob P. Laubach et al.

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ZEB1-associated drug resistance in cancer cells is reversed by the class I HDAC inhibitor mocetinostat

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HDAC8 and STAT3 repress BMF gene activity in colon cancer cells

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Histone Deacetylase 9 Promotes Angiogenesis by Targeting the Antiangiogenic MicroRNA-17-92 Cluster in Endothelial Cells

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