Review
Oncology
Asmaa Elrakaybi, Dietrich A. Ruess, Michael Luebbert, Michael Quante, Heiko Becker
Summary: Epigenetic alterations play a significant role in the biology of PDAC, providing insights into its aggressive nature and offering new avenues for personalized therapies.
Article
Biochemistry & Molecular Biology
Ignacio Silva-Llanes, Chang Hoon Shin, Jose Jimenez-Villegas, Myriam Gorospe, Isabel Lastres-Becker
Summary: The transcription factor NRF2 regulates the expression of genes encoding epigenetic regulatory factors by binding to their promoter regions containing ARE sequences. This study confirms NRF2's role in regulating histone deacetylases, DNA methyltransferases, and proteins involved in microRNA biogenesis. Additionally, NRF2 is found to be involved in the degradation of miR-155-5p through its interaction with Nfe2l2 mRNA. These findings demonstrate the epigenetic regulatory function of NRF2 and its potential implications for therapeutic strategies.
Review
Pharmacology & Pharmacy
Fahad Hussain Mohammed, Franz Cemic, Joergen Hemberger, Shibashish Giri
Summary: Epigenetic regions such as VEGF, EGFR, TGFb, DNMTs, HDAC1/2, and miRNA are innovative druggable targets for building a novel platform of drugs for preventive and regenerative skin health care. Clinical and preclinical trials are being conducted for skin regeneration using epigenetic-based small molecules. Epigenetic writers, eraser targets, and epigenetic readers will play a crucial role in skin regenerative therapy in the near future.
DRUG DISCOVERY TODAY
(2023)
Review
Cell Biology
Elena G. Pasyukova, Alexander Symonenko, Olga Y. Rybina, Alexander M. Vaiserman
Summary: Developing interventions to improve healthspan is a priority for academic and public health authorities. Geroscience focuses on targeting aging as an effective way to combat age-related disorders. Epigenome-targeted interventions in geroscience research show promise in preventing and treating various aging-related conditions.
AGEING RESEARCH REVIEWS
(2021)
Article
Chemistry, Medicinal
Bo Han, Mengfei Wang, Jiayi Li, Qiushi Chen, Niubing Sun, Xuezhi Yang, Qingwei Zhang
Summary: Many populations worldwide suffer from CNS diseases such as brain tumors, neurodegenerative diseases, and stroke, with a shortage of effective drugs. Histone deacetylases (HDACs) have been extensively studied for their role and therapeutic benefits in the CNS. Recent attention has been given to HDACs as potential drug targets for CNS diseases. This review summarizes the applications of HDACis in CNS diseases and discusses the challenges in developing HDACis with different structures and better blood-brain barrier permeability, in order to promote the development of more effective bioactive HDACis for CNS disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Immunology
Mahdieh Mehrpouri, Atieh Pourbagheri-Sigaroodi, Davood Bashash
Summary: This article outlines the role of epigenetic modulations, particularly histone deacetylases, in hematologic malignancies and their therapeutic potential. Research suggests that HDACs play a significant role in hematopoiesis and the development of blood cancers.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Stefano Ciaco, Viola Mazzoleni, Aqib Javed, Sylvia Eiler, Marc Ruff, Marc Mousli, Mattia Mori, Yves Mely
Summary: UHRF1, a nuclear multi-domain protein overexpressed in various human cancer types, can be inhibited by two new compounds, AMSA2 and MPB7, which prevent UHRF1/DNMT1 interaction during DNA replication, reduce overall DNA methylation, and induce cell death specifically in cancer cell lines with high levels of UHRF1. These compounds show promise as anti-cancer drugs targeting UHRF1 due to their specificity and effectiveness.
BIOORGANIC CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
David Rodriguez
Summary: Abusive alcohol consumption has a remarkable impact on human health, causing millions of deaths annually. Alcohol Use Disorder is a chronic disease characterized by compulsive alcohol drinking, and research on the genetic and epigenetic mechanisms behind this disease is crucial for developing new therapeutic approaches.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Review
Genetics & Heredity
Mohd Amir, Saleem Javed
Summary: Chronic myeloid leukemia is influenced by genetic and epigenetic factors, and treatment strategies include the use of targeted drugs and epigenetic inhibitors in combination. Resistance to treatment remains a challenge, necessitating the search for new therapeutic approaches.
FRONTIERS IN GENETICS
(2021)
Article
Nutrition & Dietetics
Afshin Zand, Sodbuyan Enkhbilguun, John M. Macharia, Ferenc Budan, Zoltan Gyongyi, Timea Varjas
Summary: In recent years, synthetic food colorants have shown wider properties compared to natural equivalents, but their health impact is still not well understood. This study aimed to determine the long-term effects of tartrazine, a commonly used artificial food colorant, on NMRI mice. The results showed significant upregulation of genes in various organs following tartrazine intake, suggesting possible associations with carcinogenesis and neurological disorders.
Review
Chemistry, Medicinal
Suvankar Banerjee, Sandip Kumar Baidya, Nilanjan Adhikari, Tarun Jha, Balaram Ghosh
Summary: Epigenetic modulations by HDACs are associated with various diseases. Developing specific HDAC inhibitors with high potency and selectivity, such as hydrazide-based compounds, is crucial for the treatment of diverse diseases. This article provides detailed information on the structure-activity relationship of existing hydrazide-based HDAC inhibitors, which can be utilized for the development of promising drug candidates in the future.
CURRENT TOPICS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Jessica L. Dennison, Hassan Al-Ali, Claude-Henry Volmar, Shaun Brothers, Justin Watts, Claes Wahlestedt, Ines Lohse
Summary: This study identified several epigenetic compounds with high anti-leukemia cell activity in samples from acute myeloid leukemia patients, despite the molecular diversity of the disease, suggesting that AML is predominantly an epigenetic disease and similar epigenetic mechanisms may underlie disease development and progression in all patients.
Review
Oncology
Eugenia Passaro, Chiara Papulino, Ugo Chianese, Antonella Toraldo, Raffaella Congi, Nunzio Del Gaudio, Maria Maddalena Nicoletti, Rosaria Benedetti, Lucia Altucci
Summary: Autophagy is a crucial intracellular catabolic mechanism involved in cancer, with the potential to either promote or prevent tumorigenesis. HDAC6 serves as a key regulator of autophagy, and inhibitors targeting this enzyme may be used as adjunctive therapy in cancer treatment.
Article
Oncology
Bernhard Biersack, Sibel Polat, Michael Hoepfner
Summary: Histone deacetylases (HDACs) are epigenetic regulators that affect chromatin condensation and cancer proliferation. HDAC inhibitors are promising drugs for cancer treatment. However, there are limitations and resistance issues in clinical application, leading to the search for new HDAC inhibitors. Kinase inhibitors, when used in combination with HDAC inhibitors, show synergistic anticancer effects.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Chemistry, Medicinal
Mariana Brutt Pacheco, Vania Camilo, Nair Lopes, Filipa Moreira-Silva, Margareta P. Correia, Rui Henrique, Carmen Jeronimo
Summary: The combined treatment of DNA methylation inhibitor hydralazine and histone deacetylase inhibitors panobinostat and valproic acid showed synergistic growth inhibitory effects on prostate cancer cells, particularly in DU145 cells. This suggests that these drugs may be potential therapeutic tools to counteract the progression of prostate cancer.
Article
Multidisciplinary Sciences
Shigeru Matsuda, Takehiro Yasukawa, Yuriko Sakaguchi, Kenji Ichiyanagi, Motoko Unoki, Kazuhito Gotoh, Kei Fukuda, Hiroyuki Sasaki, Tsutomu Suzuki, Dongchon Kang
SCIENTIFIC REPORTS
(2018)
Article
Medicine, Research & Experimental
Motoko Unoki, Hironori Funabiki, Guillaume Velasco, Claire Francastel, Hiroyuki Sasaki
JOURNAL OF CLINICAL INVESTIGATION
(2019)
Article
Cell Biology
Sharmin Aktar, Hiroyuki Sasaki, Motoko Unoki
Article
Cell Biology
Hiroaki Ohishi, Wan Kin Au Yeung, Motoko Unoki, Kenji Ichiyanagi, Kei Fukuda, Shoji Maenohara, Kenjiro Shirane, Hatsune Chiba, Takashi Sado, Hiroyuki Sasaki
Article
Biochemistry & Molecular Biology
Satomi Kori, Tomohiro Jimenji, Toru Ekimoto, Miwa Sato, Fumie Kusano, Takashi Oda, Motoko Unoki, Mitsunori Ikeguchi, Kyohei Arita
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Motoko Unoki, Jafar Sharif, Yuichiro Saito, Guillaume Velasco, Claire Francastel, Haruhiko Koseki, Hiroyuki Sasaki
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Takuya Morikawa, Hiroaki Ohishi, Kengo Kosaka, Tomofumi Shimojo, Akihiro Nagano, Itsuki Taniguchi, Ryuta Fujioka, Kosei Moriyama, Motoko Unoki, Masatomo Takahashi, Motonao Nakao, Yoshihiro Izumi, Takeshi Bamba, Hiroyuki Sasaki, Shiroh Miura, Hiroki Shibata
Summary: The novel homozygous 4-bp deletion in DDHD1 was identified as responsible for spastic paraplegia type 28 (SPG28). Knockout mice with a premature stop codon similar to the patient showed decreased foot-base angle and reduced LPI 20:4 (sn-2) levels in the cerebra. Changes in gene expression related to nervous system and cell-cell communication were also observed, suggesting a potential role of reduced downstream signaling in the pathogenesis of SPG28.
BIOSCIENCE REPORTS
(2021)
Review
Cell Biology
Motoko Unoki
Summary: ICF syndrome is a rare genetic disorder characterized by the frequent appearance of multiradial chromosomes in activated lymphocytes, which may result from mutations in DNMT3B, ZBTB24, CDCA7, or HELLS genes. Defects in DNA methylation and impaired maintenance DNA methylation could lead to chromosomal abnormalities and instability in patients with this syndrome.
Article
Biochemistry & Molecular Biology
Guillaume Velasco, Damien Ulveling, Sophie Rondeau, Pauline Marzin, Motoko Unoki, Valerie Cormier-Daire, Claire Francastel
Summary: DNA methylation profiling is used to improve diagnosis of patients with inherited neurodevelopmental disorders and guide mutation screening. Mutations in enzymes with similar or intertwined functions can lead to distinct DNAme signatures and consequences, highlighting functional links between different enzymes and suggesting possible redundant or complementary functions in humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Surgery
Naoki Haratake, Qingjiang Hu, Tatsuro Okamoto, Tomoko Jogo, Gouji Toyokawa, Fumihiko Kinoshita, Tomoyoshi Takenaka, Tetsuzo Tagawa, Norifumi Iseda, Shinji Itoh, Yuichi Yamada, Yoshinao Oda, Mototsugu Shimokawa, Chie Kikutake, Mikita Suyama, Motoko Unoki, Hiroyuki Sasaki, Masaki Mori
Summary: Through RNA-sequencing and TCGA dataset analysis, SLC38A7 was identified as a potential therapeutic target for SCC, with its high expression significantly associated with patient prognosis. Immunohistochemical analysis further confirmed the importance of SLC38A7 in SCC patients.
Review
Multidisciplinary Sciences
Motoko Unoki, Hiroyuki Sasaki
Summary: The UHRF protein family has multiple regulatory proteins that sense modification status of DNA and/or proteins and catalyze the ubiquitylation of target proteins. They play important roles in various biological processes and have different expression patterns and functions in mammals.
PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Motoko Unoki, Guillaume Velasco, Satomi Kori, Kyohei Arita, Yasukazu Daigaku, Wan Kin Au Yeung, Akihiro Fujimoto, Hirofumi Ohashi, Takeo Kubota, Kunio Miyake, Hiroyuki Sasaki
Summary: This study identified UHRF1 as a novel causative gene of Immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. By analyzing a patient with atypical symptoms, two previously unreported mutations in the UHRF1 gene were identified, which led to abnormal methylation and protein conformation changes. Through further analysis of patient cells and protein interactions, the importance of UHRF1 in the regulation of CG methylation was confirmed.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biology
Shuhei Uemura, Shoji Maenohara, Kimiko Inoue, Narumi Ogonuki, Shogo Matoba, Atsuo Ogura, Mayuko Kurumizaka, Kazuo Yamagata, Jafar Sharif, Haruhiko Koseki, Koji Ueda, Motoko Unoki, Hiroyuki Sasaki
Summary: In this study, the researchers found that the specific knockout of the Uhrf1 gene in oocytes affects chromosome segregation, cleavage division, and preimplantation viability in mice. Further investigations showed that these phenotypes were associated with cytoplasmic defects and not nuclear defects. Proteomic analysis of the knockout oocytes revealed down-regulation of proteins related to microtubules and disorganization of the cytoplasmic architecture, including mislocalization of mitochondria, endoplasmic reticulum, and maternal complex components.
LIFE SCIENCE ALLIANCE
(2023)
Article
Genetics & Heredity
Kugui Yoshida-Tanaka, Ko Ikemoto, Ryoji Kuribayashi, Motoko Unoki, Takako Takano, Akihiro Fujimoto
Summary: This study analyzed the structures and biological impacts of a complex congenital chromosome abnormality using genomics, transcriptomics, and DNA methylation analyses. The analysis provided insights into the mechanism underlying the generation of the extra chromosome and its pathogenic roles, including overexpression of genes and hypermethylation of the centromeric region.
Meeting Abstract
Biochemistry & Molecular Biology
T. Morikawa, S. Miura, H. Ohishi, K. Kosaka, T. Shimojo, A. Nagano, R. Fujioka, K. Moriyama, M. Unoki, M. Takahashi, M. Nakao, Y. Izumi, T. Bamba, H. Sasaki, H. Shibata
EUROPEAN JOURNAL OF HUMAN GENETICS
(2019)
