Controlling access to genomic information and maintaining its stability are key aspects of cell life. Histone acetylation is a reversible epigenetic modification that allows access to DNA and the assembly of protein complexes that regulate mainly transcription but also other activities. Enzymes known as histone deacetylases (HDACs) are involved in the removal of the acetyl-group or in some cases of small hydrophobic moieties from histones but also from the non-histone substrate. The main achievement of HDACs on histones is to repress transcription and promote the formation of more compact chromatin. There are 18 different HDACs encoded in the human genome. Here we will discuss HDAC4, a member of the class IIa family, and its possible contribution to cancer development.
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http://dx.doi.org/10.3389/fmolb.2023.1116660 | DOI Listing |
Clin Epigenetics
November 2024
Institute for Stem Cell Biology, RWTH Aachen University Medical School, 52074, Aachen, Germany.
Background: Cancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment and play a critical role in cancer progression. Numerous studies have identified significant molecular differences between CAFs and normal tissue-associated fibroblasts (NAFs). In this study, we isolated CAFs and NAFs from liver tumors and conducted a comprehensive analysis of their DNA methylation profiles, integrating our finding with data from studies on other cancer types.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
November 2024
Department of Gynecology, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410000, Hunan, China.
To investigate whether Tasquinimod can influence cisplatin resistance in drug-resistant ovarian cancer (OC) cell lines by regulating histone deacetylase 4 (HDAC4) or p21, we explored its effects on the cell cycle, and associated mechanisms. RT-PCR and Western blot analyses, flow cytometry, CCK8 assay, and immunofluorescence were utilized to investigate the effects of Tasquinimod on gene expression, cell cycle, apoptosis, viability, and protein levels in OC cells. The results showed that Tasquinimod inhibited cell viability and promoted apoptosis in SKOV3/DDP (cisplatin) and A2780/DDP cells more effectively than DDP alone.
View Article and Find Full Text PDFTransl Oncol
January 2025
Department of Gastroenterology, Shanghai Eighth People's Hospital, Xuhui Branch of Shanghai Sixth People's Hospital, 20030, China. Electronic address:
TGF-β signaling pathway has been demonstrated to be closely related to chemoresistance, which is the major cause of recurrence and poor outcome in colorectal cancer (CRC), however, the comprehensive epigenetic landscape that functionally implicates in the regulation of TGF-β pathway-associated chemoresistance has not yet well established in CRC. In our study, chromatin immunoprecipitation sequencing (ChIP-seq) and Western blot were employed to investigate epigenetic modifications for histones in response to TGF-β1 intervene. We found that the activation of the TGF-β pathway was characterized by genome-wide high levels of H3K9ac and H3K18ac.
View Article and Find Full Text PDFComb Chem High Throughput Screen
October 2024
Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Background: Gastric cancer, one of the most familiar adenocarcinomas of the gastrointestinal tract, ranks third in the world in cancer-related deaths. Traditional Chinese medicine can suppress the growth of tumors, and the underlying mechanism may be associated with the tumor microenvironment. Here, we investigated the anti-cancer effects of the Qingrexiaoji recipe on gastric cancer and the underlying molecular mechanism.
View Article and Find Full Text PDFBioorg Chem
December 2024
Department of Chemical Engineering and Biotechnology, University of Applied Sciences, 64295 Darmstadt, Germany. Electronic address:
Human histone deacetylase 4 (HDAC4) belongs to class IIa of the zinc-dependent histone deacetylases. HDAC4 is an established target for various indication areas, in particular Huntington's disease, heart failure and cancer. To reduce unwanted side effects, it is advantageous to develop isozyme-selective inhibitors, which poses a major challenge due to the highly conserved active centers of the HDAC family.
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