Review
Biochemistry & Molecular Biology
Futaba Inoue, Kenbun Sone, Yusuke Toyohara, Yu Takahashi, Asako Kukita, Aki Hara, Ayumi Taguchi, Michihiro Tanikawa, Tetsushi Tsuruga, Yutaka Osuga
Summary: Epigenetic changes play a crucial role in endometrial cancer, including DNA methylation and histone modification. There are currently inhibitors targeting epigenetic regulators in preclinical studies and clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Asad Mohammad, Sudhakar Jha
Summary: Epigenetic modifications, such as DNA methylation and histone modification, play a crucial role in cancer progression and metastasis. Inhibitors targeting deregulated enzymes can reverse these modifications and show promising results in cancer therapeutics.
Article
Biochemistry & Molecular Biology
Raul F. Perez, Juan Ramon Tejedor, Pablo Santamarina-Ojeda, Virginia Lopez Martinez, Rocio G. Urdinguio, Lucia Villamanan, Ana Paula Candiota, N. Mi Vidal Sarro, Marta Barradas, Pablo Jose Fernandez-Marcos, Manuel Serrano, Agusin F. Fernandez, Mario F. Fraga
Summary: The study found parallel epigenetic alterations in aging and cancer, with potential differences in DNA hypomethylation. While most observations came from mouse models, systematic comparisons of human and mouse epigenetic patterns in disease context are lacking. The research suggests the conservation of specific cancer and aging epigenomic signatures in human and mouse, indicating the functional consequences of these alterations at multiple levels of genomic regulation.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Review
Chemistry, Medicinal
Amir Ajoolabady, Hamid Aslkhodapasandhokmabad, Yuan Zhou, Jun Ren
Summary: This article discusses the pathogenesis of alcohol-related liver disease (ARLD) and alcoholic liver disease (ALD), with a focus on the role of epigenetic factors in the development of liver disorders. Through cellular and animal model studies, the alcohol-induced epigenetic modifications (AIEM) and their relationship with liver diseases are explored, and epigenetics-based therapeutic options for managing ARLD and ALD are proposed.
MEDICINAL RESEARCH REVIEWS
(2022)
Review
Plant Sciences
Justin Su, Zhujun Yao, Yixuan Wu, Joohyun Lee, Jeeyon Jeong
Summary: This article mainly introduces the latest understanding of chromatin-based regulation of iron homeostasis in plants, highlighting recent studies in Arabidopsis and rice. Understanding iron homeostasis in plants is crucial as it is relevant to fundamental biological questions, agriculture, biofortification, and human health.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Cell Biology
Dipanwita Das, Nandini Karthik, Reshma Taneja
Summary: Inflammation is a crucial immune response against infection and tissue damage, but chronic inflammation is linked to cancer development. Immune cells produce inflammatory mediators to facilitate tumor growth, while aberrant expression of inflammatory factors by tumor cells recruits immune cells for mutual crosstalk, creating a conducive environment for tumor growth.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jing Sui, Wenliang Qiao, Xinrong Xiang, Youfu Luo
Summary: This article describes the epigenetic changes that occur in the pathogen Mycobacterium tuberculosis and its host during infection, including DNA methylation, histone modification, and microRNA. It summarizes the research progress in drug discovery and tuberculosis diagnosis, providing new ideas and strategies to combat drug-resistant tuberculosis.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Immunology
Avinash Khadela, Vivek P. Chavda, Humzah Postwala, Yesha Shah, Priya Mistry, Vasso Apostolopoulos
Summary: Tuberculosis is a highly challenging and chronic infection that requires the action of the host's immune system. Epigenetic modification plays a crucial role in the pathophysiology and treatment of tuberculosis, but there are still gaps in the research.
Review
Plant Sciences
Kajal Samantara, Aalok Shiv, Lorenna Lopes de Sousa, Karansher Singh Sandhu, Parichita Priyadarshini, Sourav Ranjan Mohapatra
Summary: Epigenetics is an important mechanism that can help plants cope with various stressors by altering gene expression without involving changes in DNA sequences. It provides diversity to aid plants in responding to the impacts of climate change.
ENVIRONMENTAL AND EXPERIMENTAL BOTANY
(2021)
Review
Genetics & Heredity
Sonam Tulsyan, Mehreen Aftab, Sandeep Sisodiya, Asiya Khan, Atul Chikara, Pranay Tanwar, Showket Hussain
Summary: The global cancer cases and mortality rates are increasing, and efficient biomarkers are needed for accurate screening and diagnosis. Alterations in epigenetic marks may serve as potential biomarkers for early cancer detection. This review discusses the key epigenetic mechanisms and their deregulation in cancer etiology, exploring the future prospects of cancer precision medicine.
FRONTIERS IN GENETICS
(2022)
Review
Biochemistry & Molecular Biology
Valeria Pietropaolo, Carla Prezioso, Ugo Moens
Summary: Tumor viruses such as HTLV-1, HCV, MCPyV, HR-HPVs, EBV, KSHV, and HBV play a role in approximately 15% of all human cancers, using similar mechanisms to convey cancer hallmarks to infected cells. Perturbed gene expression and epigenetic processes, including DNA methylation and histone modification, are key mechanisms in virus-induced carcinogenesis. Increasing evidence shows that oncoviruses cause epigenetic modifications which are crucial in cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
R. E. Irwin, C. Scullion, S. J. Thursby, M. Sun, A. Thakur, L. Hilman, B. Callaghan, P. D. Thompson, D. J. McKenna, S. B. Rothbart, Guoliang Xu, C. P. Walsh
Summary: While the importance of epigenetic mechanisms such as DNA methylation and histone modification in gene suppression is known, there is still limited understanding of their interplay. The UHRF1 protein has been shown to interact with both DNA methylation and repressive chromatin marks, but its primary function in humans was unclear. In this study, stable knockdowns of UHRF1 in human fibroblasts revealed a loss of DNA methylation across the entire genome, accompanied by the activation of genes involved in innate immune signaling due to the presence of viral RNA from retrotransposable elements.
Article
Biochemistry & Molecular Biology
Sreepoorna Pramodh, Ritu Raina, Arif Hussain, Sali Abubaker Bagabir, Shafiul Haque, Syed Tasleem Raza, Mohammad Rehan Ajmal, Shalini Behl, Deepika Bhagavatula
Summary: This study analyzed the epigenetic modulatory behavior of luteolin on HeLa cells and found that luteolin can inhibit migration and colony formation in HeLa cells. It can also reactivate silenced tumor suppressor genes by modulating DNA methylation, enzyme activity, and global DNA methylation. Therefore, luteolin-targeted epigenetic alterations provide a potential approach for cancer prevention and intervention.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Fei Xu, Wenhui Li, Xiao Yang, Lixin Na, Linjun Chen, Guobin Liu
Summary: Osteoporosis is a metabolic disease characterized by decreased bone mineral density and bone microstructure destruction. Epigenetics, including DNA methylation, histone modification, and non-coding RNAs, play an important role in post-transcriptional regulation and are closely related to bone metabolism processes such as osteogenic differentiation and bone remodeling. Abnormal epigenetic regulation can lead to bone metabolism-related diseases like osteoporosis, highlighting the importance of understanding epigenetic mechanisms for potential treatments.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Jack Crouch, Maria Shvedova, Rex Jeya Rajkumar Samdavid Thanapaul, Vladimir Botchkarev, Daniel Roh
Summary: Senescence is a complex cellular stress response that leads to loss of proliferative capacity and changes in secretory pattern. Transcriptional regulation of multiple genes and epigenetic alterations to DNA and chromatin play crucial roles in the induction and maintenance of senescence. This review highlights the changes in chromatin, DNA methylation, histone alterations, and the specific epigenetic regulation of the senescence-associated secretory phenotype (SASP).
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
Hematology
Antonio Lahera, Pilar Lopez-Nieva, Hernan Alarcon, Jose L. Marin-Rubio, Maria A. Cobos-Fernandez, Pablo Fernandez-Navarro, Agustin F. Fernandez, Laura Vela-Martin, Isabel Sastre, Sara Ruiz-Garcia, Pilar Llamas, Jose L. Lopez-Lorenzo, Javier Cornago, Javier Santos, Jose Fernandez-Piqueras, Maria Villa-Morales
Summary: Despite frequent alterations in the JAK/STAT pathway in T-ALL/LBL, there is currently no approved therapy for patients with constitutive JAK/STAT signaling. This study identifies SOCS3 hypermethylation as a recurrent event in T-ALL/LBL and demonstrates its potential as a therapeutic target by counteracting the constitutive activation of the JAK/STAT pathway through different molecular mechanisms.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Juan Jose Alba-Linares, Raul F. Perez, Juan Ramon Tejedor, David Bastante-Rodriguez, Francisco Ponce, Nuria Garcia Carbonell, Rafael Gomez Zafra, Agustin F. Fernandez, Mario F. Fraga, Empar Lurbe
Summary: Maternal obesity or gestational diabetes mellitus are significant risk factors for cardiometabolic diseases in children. A study on the DNA methylation landscape of children born to mothers with obesity and gestational diabetes found abundant methylation changes during the first 6 months of life, associated with genes and pathways involved in fatty acid metabolism, developmental processes, and mitochondrial bioenergetics. The study also revealed an interaction between developmental methylation changes and maternal metabolic alterations.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Aleix Noguera-Castells, Carlos A. Garcia-Prieto, Damiana Alvarez-Errico, Manel Esteller
Summary: DNA methylation, a well-studied epigenetic mark, plays a critical role in gene regulation and is altered in cancer and other diseases. The newly developed 900K EPIC v2 microarray provides significant improvements in coverage and includes additional probes for DNA cis-regulatory regions. Validation studies demonstrate the reproducibility and versatility of this updated tool for studying the DNA methylome.
Article
Biochemistry & Molecular Biology
David Ortega-Alarcon, Rafael Claveria-Gimeno, Sonia Vega, Olga C. Jorge-Torres, Manel Esteller, Olga Abian, Adrian Velazquez-Campoy
Summary: Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark that interacts with MeCP2 in a distinct mode with a specific thermodynamic signature. Mutations associated with Rett syndrome alter the interaction between MeCP2 and dsDNA in a cytosine modification-specific manner, which may be correlated with disease onset time and clinical severity score.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(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)
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
Oncology
Pablo Santamarina-Ojeda, Juan Ramon Tejedor, Raul F. Perez, Virginia Lopez, Annalisa Roberti, Cristina Mangas, Agustin F. Fernandez, Mario F. F. Fraga
Summary: Glioblastoma (GBM) is an aggressive and heterogeneous type of cancer, posing challenges in developing effective treatments. Incorporating molecular features into diagnosis has improved categorization of GBM subtypes, revealing subtype-specific vulnerabilities. By integrating gene expression and DNA methylation data, potential vulnerabilities in GBM patients were identified, implicating the AP-1, SMAD3, and RUNX1/RUNX2 pathways in tumor development. Inhibition of these pathways, with or without the chemotherapy agent temozolomide, led to impaired tumor growth, particularly in the aggressive, mesenchymal-like subtype. These findings have implications for personalized therapeutic approaches.
MOLECULAR ONCOLOGY
(2023)
