Review
Biochemistry & Molecular Biology
Svetlana Demyanenko, Valentina Dzreyan, Svetlana Sharifulina
Summary: Cerebral ischemia is the second leading cause of death worldwide, requiring multimodal stroke therapy. Histone deacetylase inhibitors have shown to be effective in protecting the brain from ischemic damage by inducing neurogenesis and angiogenesis in damaged brain areas, promoting functional recovery after stroke.
Article
Biotechnology & Applied Microbiology
Nando D. Das, Jen-Chien Chang, Chung-Chau Hon, S. Thomas Kelly, Shinsuke Ito, Marina Lizio, Bogumil Kaczkowski, Hisami Watanabe, Keisuke Katsushima, Atsushi Natsume, Haruhiko Koseki, Yutaka Kondo, Aki Minoda, Takashi Umehara
Summary: This study found that H4K5acK8ac and H3K27ac signals have some overlap in binding to the super-enhancer transcription factor BRD4 at higher levels, but they also have distinct specificities, especially in glioblastoma stem-like cell lines. Deletion of H4K5acK8ac-preferred super-enhancers associated with MYCN and NFIC resulted in a reduction in stem-like properties.
Article
Chemistry, Medicinal
Xingrui He, Zi Hui, Li Xu, Renren Bai, Yuan Gao, Zongcheng Wang, Tian Xie, Xiang-Yang Ye
Summary: Histone deacetylases (HDACs) are important enzymes involved in the removal of acetyl groups from lysine residues, and have shown potential therapeutic applications in cancer and various diseases. There are currently numerous HDAC inhibitors under clinical investigation, aiming to provide up-to-date information for drug discovery programs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Fengyi Guo, Hongjing Wang
Summary: This review summarizes the classification and mechanisms of action of histone deacetylase and the clinical application of their inhibitors in ovarian cancer. Histone deacetylase inhibitors show promising potential as anti-cancer drugs, and combination therapy with other anticancer drugs for synergistic effects can improve efficacy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Xingrui He, Hang Zhang, Yingqian Zhang, Yang Ye, Shuo Wang, Renren Bai, Tian Xie, Xiang-Yang Ye
Summary: Post-translational modifications (PTMs) of histone by histone demethylases (KDMs) are important for gene expression regulation and are implicated in the development of various human cancers and diseases. This review surveys the latest small-molecule inhibitors of KDMs, focusing on literature since 2018, including inhibitors of lysine-specific demethylases (LSD or KDM1) and JmjC family N-methyl lysine demethylases (JmjC KDMs, i.e. KDM2-7). The review also discusses drug design strategy, structure-activity relationships (SARs), analysis of co-crystal structures, and mechanisms of action (MOA).
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
He-ming Huang, Shi-jie Fan, Xiao-ru Zhou, Yan-jun Liu, Xiao Li, Li-ping Liao, Jing Huang, Cui-cui Shi, Liang Yu, Rong Fu, Jian-gao Fan, Yuan-yuan Zhang, Cheng Luo, Guang-ming Li
Summary: Givinostat demonstrated therapeutic potential in treating nonalcoholic steatohepatitis (NASH) by alleviating inflammation and attenuating hepatic fibrosis, as shown in both in vivo and in vitro studies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Oncology
Melanie R. Muller, Aaron Burmeister, Margaretha A. Skowron, Alexa Stephan, Felix Bremmer, Gamal A. Wakileh, Patrick Petzsch, Karl Kohrer, Peter Albers, Daniel Nettersheim
Summary: This study identified seven drugs targeting epigenetic modifiers to treat cisplatin-resistant GCTs. Mass spectrometry-based analyses revealed effects beyond the expected mode-of-action of each drug, suggesting a wider spectrum of activity. Additionally, the study characterized the effects of each drug on the transcriptome of GCT cells and identified common deregulations in gene expression of ion transporters and DNA-binding factors.
CLINICAL EPIGENETICS
(2022)
Review
Pharmacology & Pharmacy
Yuan Meng, Juan Du, Ning Liu, Yuanyuan Qiang, Lifei Xiao, Xiaobing Lan, Lin Ma, Jiamei Yang, Jianqiang Yu, Guangyuan Lu
Summary: Depression is a serious mental illness with multiple causes. Previous studies have shown that it is influenced by environmental and genetic factors. This review explores the relationship between histone deacetylases (HDACs) and depression, and discusses the potential therapeutic use of HDAC inhibitors (HDACis) in treating depression.
JOURNAL OF DRUG TARGETING
(2023)
Article
Agronomy
Sasipriya Sasikumar, Banur Marulasiddappa Dushyanthakumar, Shankarappa Sridhara, Nagarajappa Adivappar, Harish Babu Bheemanapalli Nagraja, Ahmed M. El-Shehawi, Salman Aloufi, Mohammed Alqurashi, Hosam O. Elansary, Khalid M. Elhindi, Eman A. Mahmoud
Summary: This study investigated the effects of Trichostatin A (TSA) on the morphological variations in okra. The results showed that TSA treatment had a negative impact on the growth and development of okra, including inhibited seedling emergence, malformed plants, abnormal flower development, and pollen sterility. However, under specific doses and incubation periods, TSA treatment can induce epigenetic variations in okra without significantly compromising its growth and vigor parameters.
Review
Biochemistry & Molecular Biology
Yi Ching Esther Wan, Kui Ming Chan
Summary: Oncohistones have become a new focus in cancer epigenetics research, with recent studies uncovering thousands of histone mutations in cancer. Unlike previously identified oncohistones, the newly discovered mutations are located within the histone fold domain and impact gene expression through different mechanisms. Recent characterization of selected H2B has highlighted previously unappreciated roles of oncohistones in nucleosome stability, chromatin accessibility, and chromatin remodeling.
Review
Clinical Neurology
Vaidya Govindarajan, Ashish H. Shah, Long Di, Sarah Rivas, Robert K. Suter, Daniel G. Eichberg, Evan Luther, Victor Lu, Alexis A. Morell, Michael E. Ivan, Ricardo J. Komotar, Nagi Ayad, Macarena De la Fuente
Summary: This article is a systematic review of the clinical application of epigenetic therapies in the treatment of IDH-mutant gliomas. The results show that IDH inhibitors have a good safety profile and efficacy, while histone deacetylase inhibitors have a lower safety profile. Preliminary data suggest that epigenetic therapies may have good tolerability and efficacy in controlling nonenhancing lesions.
WORLD NEUROSURGERY
(2022)
Review
Oncology
Anna Wawruszak, Marta Halasa, Estera Okon, Wirginia Kukula-Koch, Andrzej Stepulak
Summary: Breast cancer is the most common malignancy affecting women worldwide, with valproic acid showing promising potential in inhibiting cancer cell proliferation. Studies have demonstrated that VPA, a member of the group of histone deacetylase inhibitors, can modulate multiple signaling pathways and improve the effectiveness of current treatment methods for breast cancer.
Review
Pharmacology & Pharmacy
Hae Jin Kee, Inkyeom Kim, Myung Ho Jeong
Summary: This article provides an overview of the pathogenesis of hypertension, current anti-hypertensive drugs, and the need for novel drugs. It focuses on the role and regulatory mechanisms of HDACs in hypertension and discusses the progress in developing HDAC inhibitors as potential therapeutic targets.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Microbiology
H. Martin Kramer, Michael F. Seidl, Bart P. H. J. Thomma, David E. Cook
Summary: Analyzing the H3K27me3 and transcription data of the plant-pathogenic fungus Verticillium dahliae grown in three in vitro cultivation media, it was found that many H3K27me3 domains displayed stable profiles across different conditions, while some differentially transcribed genes were associated with local quantitative differences in H3K27me3 ChIP-seq signals. This suggests that while H3K27me3 may play a role in transcriptional variation, it is not a universal regulator of differential transcription in response to environmental cues.
Review
Endocrinology & Metabolism
Lindsay Moritz, Saher Sue Hammoud
Summary: This article explores the molecular mechanisms underlying male fertility and the process of chromatin remodeling. It points out the current gaps in understanding of the chromatin remodeling process and suggests future research directions to enhance our knowledge of the histone-to-protamine exchange and the etiology of idiopathic male infertility.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Oncology
Veronica Davalos, Manel Esteller
Summary: Cancer development is caused by changes in the structure and function of the genome. Epigenetic alterations regulate gene expression programs that promote tumorigenesis and can be used as useful tools in clinical decision making. Unlike genetic changes, epigenetic modifications can be reversed, making them an attractive target for drug development.
CA-A CANCER JOURNAL FOR CLINICIANS
(2023)
Review
Oncology
Iris van der Strate, Fatemeh Kazemzadeh, Iris D. Nagtegaal, Debbie Robbrecht, Agnes van de Wouw, Catarina S. Padilla, Saskia Duijts, Manel Esteller, F. Anthony Greco, Nicholas Pavlidis, Amir Qaseem, Petur Snaebjornsson, Sophie Veldhuijzen van Zanten, Caroline Loef
Summary: The study proposes a multi-layer classification for the diagnostic workup of CUP using the Delphi method. The recommended initial diagnostic includes history and physical examination, full blood count, serum marker analysis, biopsy of accessible lesion, CT scan, and immunohistochemical testing. Consensus was also reached on the need for an ideal diagnostic lead time for CUP patients.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Paolo Petazzi, Olga Caridad Jorge-Torres, Antonio Gomez, Iolanda Scognamiglio, Jordi Serra-Musach, Angelika Merkel, Daniela Grases, Clara Xiol, Mar O'Callaghan, Judith Armstrong, Manel Esteller, Sonia Guil
Summary: Rett syndrome is a severe neurodevelopmental disease caused by mutations in the MeCP2 gene, which affects synaptic plasticity and neuronal activity. The MeCP2 protein is critical for the proper expression of immediate-early genes (IEGs) involved in activity-dependent responses, and abnormal expression of IEGs is found in MeCP2-deficient neurons and in RTT patients. These findings highlight the importance of IEGs in synaptic development and the regulatory role of MeCP2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Jiajin Chen, Yunjie Song, Yi Li, Yongyue Wei, Sipeng Shen, Yang Zhao, Dongfang You, Li Su, Maria Moksnes Bjaanaes, Anna Karlsson, Maria Planck, Johan Staaf, Aslaug Helland, Manel Esteller, Hongbing Shen, David C. C. Christiani, Ruyang Zhang, Feng Chen
Summary: This study identified significant gene-gene interactions associated with non-small-cell lung cancer survival through a three-step analytic strategy. Two interactions were found at both the epigenetic and transcriptional levels, providing potential clues for precision treatment of NSCLC.
MOLECULAR ONCOLOGY
(2023)
Review
Genetics & Heredity
Ines Orsolic, Arnaud Carrier, Manel Esteller
Summary: Cancer was once believed to be solely genetic, but now it is known that dysregulated genetic and epigenetic mechanisms work together in cancer development. Recently, the epitranscriptome, which refers to chemical modifications of RNA molecules, has been found to play a role in regulating RNA function. Specific enzymes responsible for these modifications, known as RMPs, are being investigated for their potential as therapeutic targets or diagnostic markers in cancer. The study of epitranscriptomics has revealed the critical role of RNA modifications in cellular pathways and their potential importance in cancer treatment.
TRENDS IN GENETICS
(2023)
Article
Pharmacology & Pharmacy
Daniela S. Contartese, Manuel Rey-Funes, Rafael Pelaez, Manuel Solino, Juan C. Fernandez, Ronan Nakamura, Nicolas S. Ciranna, Anibal Sarotto, Veronica B. Dorfman, Juan J. Lopez-Costa, Jose M. Zapico, Ana Ramos, Beatriz de Pascual-Teresa, Ignacio M. Larrayoz, Cesar F. Loidl, Alfredo Martinez
Summary: We investigated the protective effects of the hypothermia mimetic molecule, zr17-2, on ocular traumatism. Our study showed that intravitreal injection of zr17-2 significantly reduced retinal damage and preserved eye function after trauma.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Miriam Gene, Miriam Cuatrecasas, Irene Amat, Jesus Alberto Veiga, Maria Jesus Fernandez Acenero, Victoria Fuste Chimisana, Jordi Tarragona, Ismael Jurado, Rebeca Fernandez-Victoria, Carolina Martinez Ciarpaglini, Cristina Alenda Gonzalez, Carlos Zac, Pilar Ortega de la Obra, Maria Teresa Fernandez-Figueras, Manel Esteller, Eva Musulen
Summary: Colitis-associated colorectal carcinoma (CAC) in inflammatory bowel disease (IBD) is caused by p53 alterations and follows a chronic inflammation-dysplasia-cancer carcinogenesis pathway. Gastric metaplasia (GM) is described as the initial event of serrated colorectal cancer (CRC) in the colon mucosa under chronic stress. This study analyzed p53 alterations and microsatellite instability (MSI) to characterize CAC and investigate its relationship with GM. Results showed that p53 mutation pattern was present in more than half of the CAC cases, with stable (MSS) tumors being the most common and MUC5AC negative. Only six unstable (MSI-H) tumors had wild-type p53 pattern (p=0.010) and were MUC5AC positive (p=0.005). MUC5AC staining was more frequently observed in intestinal mucosa with inflammation or chronic changes than in CAC, particularly in those with wild-type p53 pattern and MSS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Editorial Material
Oncology
Maxime Janin, Manel Esteller
Summary: Mutations in splicing factors are commonly found in CLL, but other mechanisms such as METTL3 overexpression can also lead to abnormal splicing. METTL3 deposits epitranscriptomic marks in spliceosome transcripts, causing aberrant splicing, but also vulnerability to METTL3 inhibitors.
BLOOD CANCER DISCOVERY
(2023)
Meeting Abstract
Oncology
A. Martinez, A. Martin-Carnicero, M. T. Tena, M. P. Martinez-Moral
ANNALS OF ONCOLOGY
(2023)
Meeting Abstract
Oncology
J. Garcia-Sanmartin, F. Cuttitta, Y. Feng, M. E. Sunday, Y. S. Kim, A. Martinez
ANNALS OF ONCOLOGY
(2023)
Review
Oncology
Maxime Janin, Veronica Davalos, Manel Esteller
Summary: Most cancer-related deaths and illnesses can be attributed to metastasis. The role of epigenetic and epitranscriptomic changes in the origin and progression of cancer has been extensively demonstrated. These two-layer regulatory mechanisms, driven by DNA or RNA modifiers, are finely controlled in normal tissue but dysregulated in cancer. Understanding these mechanisms could have important clinical implications for prevention and management of advanced malignancies. Reversing these epi-alterations with small molecules or inhibitors against epi-modifiers could offer novel therapeutic alternatives.
CANCER AND METASTASIS REVIEWS
(2023)
Letter
Oncology
Carlos A. Garcia-Prieto, Veronica Davalos, Manel Esteller
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Oncology
Lucia Salz, Alexander Seitz, Daniel Schaefer, Julia Franzen, Tatjana Holzer, Carlos A. Garcia-Prieto, Iris Buerger, Olaf Hardt, Manel Esteller, Wolfgang Wagner
Summary: CAR T cell expansion during culture leads to DNA hypermethylation, which downregulates the expression of genes relevant to T cell function. This hypermethylation signature can predict cell culture time and is associated with reduced long-term survival and therapeutic outcome in CAR T cell products.
Article
Biotechnology & Applied Microbiology
Nancy G. Viveros-Moreno, Mario Garcia-Lorenzana, Eduardo Pena-Mercado, Josune Garcia-Sanmartin, Judit Narro-iniguez, Marcela Salazar-Garcia, Sara Huerta-Yepez, Concepcion Sanchez-Gomez, Alfredo Martinez, Nohra E. Beltran-Vargas
Summary: This study evaluated the biocompatibility of three scaffolds made from an alginate-chitosan combination and functionalized with gold nanoparticles. The results showed that the functionalized scaffolds have improved biocompatibility and exhibit promising potential as biomaterials for tissue engineering constructs.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Edilene Siqueira, Bo-Hyun Kim, Larry Reser, Robert Chow, Kerry Delaney, Manel Esteller, Mark M. Ross, Jeffrey Shabanowitz, Donald F. Hunt, Sonia Guil, Juan Ausio
Summary: This study used a neural cell line derived from the human ventral mesencephalon, called ReNCell, and its MeCP2 knock out to investigate the changes in linker histones during neural cell differentiation. The results showed that MeCP2 played a crucial role in dendrite and axon development and exhibited extensive co-localization with linker histones. Additionally, the size of the nucleus decreased during differentiation, but the MeCP2 knock out cells showed a significant increase in nucleus size after differentiation.
