Article
Biochemistry & Molecular Biology
Omkar Suhas Vinchure, Kurt Whittemore, Deependra Kushwah, Maria A. Blasco, Ritu Kulshreshtha
Summary: miR-490 targets multiple genes to regulate telomere maintenance in GBM, exerting tumor suppressive effects, impacting stemness and senescence, activating DNA damage response, and potentially holding therapeutic significance in GBM treatment.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Oncology
Lukas Krauss, Bettina C. Urban, Sieglinde Hastreiter, Carolin Schneider, Patrick Wenzel, Zonera Hassan, Matthias Wirth, Katharina Lankes, Andrea Terrasi, Christine Klement, Filippo M. Cernilogar, Rupert Oellinger, Niklas de Andrade Kraetzig, Thomas Engleitner, Roland M. Schmid, Katja Steiger, Roland Rad, Oliver H. Kraemer, Maximilian Reichert, Gunnar Schotta, Dieter Saur, Guenter Schneider
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.
Article
Hematology
Georg Leubolt, Roland Windisch, Paul Kerbs, Sayantanee Dutta, Theresa Landspersky, Rouzanna Istvanffy, Linping Chen-Wichmann, Tobias Herold, Monica Cusan, Gunnar Schotta, Christian Wichmann, Philipp A. A. Greif, Enric Redondo Monte, Robert A. J. Oostendorp
Summary: GATA2 zinc-finger mutations are associated with various myeloid malignancies, and their specific distribution and effects indicate different mechanisms of leukemogenesis. The study found that these mutations disrupted DNA binding and had variable responses to transcriptional regulation mediated by FOG1. In addition, the mutations altered the differentiation of bone marrow cells and showed different effects depending on the specific mutation.
EXPERIMENTAL HEMATOLOGY
(2022)
Article
Cell Biology
Giuseppe Bosso, Pablo Lanuza-Gracia, Sergio Pineiro-Hermida, Merve Yilmaz, Rosa Serrano, Maria A. Blasco
Summary: BRAF(V600E) mutation is common in cancer and its expression leads to DNA damage response, inflammation, and differential changes in cell cycle and senescence-associated proteins in lung epithelia.
CELL DEATH & DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Miriam Ayora, David Fraguas, Renzo Abregu-Crespo, Sandra Recio, Maria A. Blasco, Ana Moises, Aksinya Derevyanko, Celso Arango, Covadonga M. Diaz-Caneja
Summary: The meta-analysis found that leukocyte telomere length was significantly shorter in patients with schizophrenia and related disorders compared to healthy controls, with no significant effects of age or illness duration on this difference. The results support the hypothesis of accelerated cellular aging in schizophrenia and related disorders, highlighting the need for large longitudinal studies with repeated telomere length measurements and appropriate assessments of associated factors.
MOLECULAR PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Graeme J. Thorn, Christopher T. Clarkson, Anne Rademacher, Hulkar Mamayusupova, Gunnar Schotta, Karsten Rippe, Vladimir B. Teif
Summary: The study reveals that the patterns of heterochromatin nanodomains (HNDs) can be computed and determined by the interactions between DNA sequences and protein factors, which helps explain the establishment and changes of H3K9me2/3 patterns. Predicting epigenetic regulation is an important challenge.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Paula Martinez, Raul Sanchez-Vazquez, Iole Ferrara-Romeo, Rosa Serrano, Juana M. Flores, Maria A. Blasco
Summary: By generating a mouse model for the human POT1(R117C) mutation, this study found that the mutation leads to longer telomeres and exerts dominant-negative effects at telomeres. Heterozygous mice with this mutation also develop angiosarcomas, including cardiac angiosarcomas. This research provides important insights into human cancers initiated by POT1 mutations.
Article
Multidisciplinary Sciences
Zeyang Wang, Rui Fan, Angela Russo, Filippo M. Cernilogar, Alexander Nuber, Silvia Schirge, Irina Shcherbakova, Iva Dzhilyanova, Enes Ugur, Tobias Anton, Lisa Richter, Heinrich Leonhardt, Heiko Lickert, Gunnar Schotta
Summary: Silencing of endogenous retroviruses is crucial for maintaining transcriptional and genomic integrity of cells, with DNA methylation playing a dominant role over H3K9 methylation.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Sergio Pineiro-Hermida, Paula Martinez, Giuseppe Bosso, Juana Maria Flores, Sarita Saraswati, Jane Connor, Raphael Lemaire, Maria A. Blasco
Summary: Depletion of TRF1 does not lead to interstitial lung fibrosis, highlighting the relevance of alveolar type II cells in this disease.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Jorge Sanz-Ros, Nekane Romero-Garcia, Cristina Mas-Bargues, Daniel Monleon, Juozas Gordevicius, Robert T. Brooke, Mar Dromant, Ana Diaz, Aksinya Derevyanko, Ana Guio-Carrion, Aurora Roman-Dominguez, Marta Ingles, Maria A. Blasco, Steve Horvath, Jose Vina, Consuelo Borras
Summary: This study found that treatment of old animals with ADSC-sEVs derived from young animals can improve various parameters associated with aging and reduce frailty. This treatment induces proregenerative effects and reduces oxidative stress, inflammation, and senescence in muscle and kidney. Additionally, tissue epigenetic age decreases and metabolome shifts to a youth-like pattern after this treatment.
Article
Oncology
Cristina Montero-Conde, Luis Javier Leandro-Garcia, Angel M. Martinez-Montes, Paula Martinez, Francisco J. Moya, Rocio Leton, Eduardo Gil, Natalia Martinez-Puente, Sonsoles Guadalix, Maria Curras-Freixes, Laura Garcia-Tobar, Carles Zafon, Mireia Jorda, Garcilaso Riesco-Eizaguirre, Patricia Gonzalez-Garcia, Maria Monteagudo, Rafael Torres-Perez, Veronika Mancikova, Sergio Ruiz-Llorente, Manuel Perez-Martinez, Guillermo Pita, Juan Carlos Galofre, Anna Gonzalez-Neira, Alberto Cascon, Cristina Rodriguez-Antona, Diego Megias, Maria A. Blasco, Eduardo Caleiras, Sandra Rodriguez-Perales, Mercedes Robledo
Summary: Comprehensive molecular studies were conducted on thyroid tumors to identify prognostic biomarkers. Telomere-related alterations, especially TERT and TERC, were found in aggressive tumors. Short telomeres led to reorganization in the 5p subtelomeric region, resulting in increased gene upregulation and a more relaxed chromatin configuration in the tumors.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Carlos Lopez-Otin, Maria A. Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer
Summary: Aging is driven by hallmarks that manifest with age, accelerate aging when accentuated experimentally, and can be decelerated, stopped, or reversed with therapeutic interventions. The twelve proposed hallmarks of aging include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected with each other and with the recently proposed hallmarks of health.
Article
Biochemistry & Molecular Biology
Sergio Pineiro-Hermida, Giuseppe Bosso, Raul Sanchez-Vazquez, Paula Martinez, Maria A. Blasco
Summary: Non-small cell lung cancer (NSCLC) is a leading cause of cancer death, and tumor progression is influenced by the interaction between cancer cells and the tumor microenvironment. Increased copy number and mRNA expression of TERT, a catalytic subunit of telomerase, is associated with decreased survival in NSCLC patients. Targeting telomeres may be an effective therapeutic approach in NSCLC treatment.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Emanuele Mocciaro, Roberto Giambruno, Stefano Micheloni, Filippo M. Cernilogar, Annapaola Andolfo, Cristina Consonni, Maria Pannese, Giulia Ferri, Valeria Runfola, Gunnar Schotta, Davide Gabellini
Summary: FSHD is a prevalent neuromuscular disorder associated with copy number reduction and epigenetic alterations of the D4Z4 macrosatellite on chromosome 4q35. Aberrant expression of the transcription factor DUX4 plays a key role in this disease. In this study, the authors identified the chromatin remodeling protein WDR5 as an interactor of the long non protein-coding RNA DBE-T and demonstrated its requirement for the expression of DUX4 and its targets. Targeting WDR5 rescued cell viability and myogenic differentiation of FSHD patient cells, suggesting it as a potential therapeutic target for FSHD.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Paula Martinez, Raul Sanchez-Vazquez, Arpita Saha, Maria S. Rodriguez-Duque, Sara Naranjo-Gonzalo, Joy S. Osorio-Chavez, Ana V. Villar-Ramos, Maria A. Blasco
Summary: The severity of COVID-19 increases with age, suggesting that organismal aging contributes to its fatality. Previous studies have shown that COVID-19 severity is correlated with shorter telomeres in patient's leukocytes. Lung injury is a prominent feature of acute SARS-CoV-2 infection, which can progress to lung fibrosis. In this study, we found that post-COVID-19 patients have shorter telomeres and increased lung fibrosis compared to age-matched controls with lung cancer, suggesting a link between short telomeres in ATII cells and long-term lung fibrosis in post-COVID-19 patients.