Article
Oncology
Gh. Rasool Bhat, Rajeshwer Singh Jamwal, Itty Sethi, Amrita Bhat, Ruchi Shah, Sonali Verma, Minerva Sharma, Hana Q. Sadida, Sara K. Al-Marzooqi, Tariq Masoodi, Sameer Mirza, Mohammad Haris, Muzafar A. Macha, Ammira S. Alshabeeb Akil, Ajaz A. Bhat, Rakesh Kumar
Summary: This study highlights the important relationship between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the population of Jammu and Kashmir, North India. The study found significant associations between specific variants in TERT and POT1 genes and NSCLC risk, as well as significantly shorter telomere lengths in NSCLC patients. These findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population.
Review
Biochemistry & Molecular Biology
Eleonora Vertecchi, Angela Rizzo, Erica Salvati
Summary: Telomeres, crucial for maintaining genome stability, gradually shorten over time and can determine the senescence of cells and organisms. Targeting telomere maintenance mechanisms has become an important approach for cancer treatment, as telomere length homeostasis plays a critical role in cancer development. Dysfunction in telomeres can affect intracellular signaling pathways, particularly DNA damage signaling and repair, leading to implications for cancer cell survival and proliferation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Yonggui Xiao, Danping Xu, Chonghao Jiang, Youlong Huili, Shiwen Nie, Hongfei Zhu, Guorui Fan, Xiaohai Guan
Summary: Through bioinformatics analysis, we obtained a prognostic model of telomere maintenance-related genes. Through validation with both internal and external groups, we believe that the model can accurately predict the survival of bladder cancer patients. With the help of the HPA database, we identified genes with low expression in tumor patients (ABCC9, AHNAK, DIP2C) and genes with high expression (PLOD1, SLC3A2, RUNX2, RAD9A, CHMP4C, DARS2, CLIC3, POU5F1). The model has accurate predictive power for populations with different clinical and pathological features. Clinicians can use the nomogram to easily assess patient survival rates and formulate personalized treatment plans based on prediction results, immune analysis, and drug susceptibility analysis. Different subtypes can further divide patients for more precise treatment plans.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Maria Monteagudo, Paula Martinez, Luis J. Leandro-Garcia, Angel M. Martinez-Montes, Bruna Calsina, Marta Pulgarin-Alfaro, Alberto Diaz-Talavera, Sara Mellid, Rocio Leton, Eduardo Gil, Manuel Perez-Martinez, Diego Megias, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Patricia Gonzalez, Eduardo Caleiras, Scherezade Jimenez-Villa, Giovanna Roncador, Cristina Alvarez-Escola, Rita M. Regojo, Maria Calatayud, Sonsoles Guadalix, Maria Curras-Freixes, Elena Rapizzi, Letizia Canu, Svenja Noelting, Hanna Remde, Martin Fassnacht, Nicole Bechmann, Graeme Eisenhofer, Massimo Mannelli, Felix Beuschlein, Marcus Quinkler, Cristina Rodriguez-Antona, Alberto Cascon, Maria A. Blasco, Cristina Montero-Conde, Mercedes Robledo
Summary: Recent studies have highlighted the importance of telomere maintenance mechanisms involving TERT and ATRX genes in metastatic pheochromocytoma and paraganglioma (mPPGL). In addition to validating the predictive value of TERT and ATRX in mPPGL progression, this study also identified NOP10 as a novel prognostic risk marker of mPPGLs. By analyzing 29 telomere-related genes, it was found that NOP10 plays a role in telomerase-dependent telomere length maintenance in these tumors, suggesting its potential as a new marker for identifying metastatic-risk patients. The proposal to implement NOP10 immunohistochemistry (IHC) as part of the current marker panel for PPGL patients aims to improve clinical diagnoses.
Article
Biochemistry & Molecular Biology
Ji-Yong Sung, Jae-Ho Cheong
Summary: This study classified four telomere maintenance mechanisms and demonstrated the impact of different TMMs on patient prognoses in six cancer types. The results revealed significant associations between specific TMMs and patient outcomes, as well as potential effects of master transcriptional regulators on TMM pathway selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Hiroshi Ebata, Tze Mun Loo, Akiko Takahashi
Summary: This review summarizes the unique characteristics of cancer cells, such as high proliferation and aberrant DNA damage response, and the role of telomerase and ALT in cancer regulation. It focuses on their noncanonical functions beyond telomere maintenance, as well as intercellular communication in the tumor microenvironment (TME) through the cGAS-STING pathway. Understanding the functional connection between telomere-related molecules and TME regulation is crucial for developing cancer therapeutics targeting specific pathways.
Review
Oncology
Jixuan Gao, Hilda A. Pickett
Summary: This review discusses the latest developments and strategies in targeting telomerase and ALT mechanisms for cancer treatment. It also introduces the methods for detecting these two mechanisms and their utility in clinical diagnosis. In addition to inhibiting telomere maintenance, exploiting the weaknesses of telomeres themselves can induce cell death.
NATURE REVIEWS CANCER
(2022)
Article
Biology
Kevin Hu, Mahmoud Ghandi, Franklin W. Huang
Summary: Research shows that telomerase reverse transcriptase (TERT) expression correlates with telomere content in lung, central nervous system, and leukemia cell lines. Lower telomeric content is associated with dependency of CST telomere maintenance genes, while increased dependencies of shelterin members are associated with wild-type TP53 status.
Article
Engineering, Industrial
Xiangxia Ren, Jun Zhang, Weiguo Song
Summary: Research on human safety in crowded environments is crucial for public safety, with pedestrian density affecting speed differences between walking and running pedestrians. Decision makers should take into account pedestrian density when considering evacuation strategies in different scenarios.
Article
Biochemistry & Molecular Biology
Simon Dellicour, Mandev S. Gill, Nuno R. Faria, Andrew Rambaut, Oliver G. Pybus, Marc A. Suchard, Philippe Lemey
Summary: Spatially explicit phylogeographic analyses can be conducted using a framework that employs relaxed random walks to reconstruct phylogenetic dispersal histories in continuous space. This approach, introduced 10 years ago, has provided new opportunities in the field of phylodynamics for mapping and analyzing the spatial dissemination of rapidly evolving pathogens. The authors provide a detailed guide on setting up, running, and interpreting continuous phylogeographic analyses using specific programs.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Cell Biology
Ji-Yong Sung, Jae-Ho Cheong
Summary: Telomere maintenance mechanisms (TMMs) are crucial for cell survival and homeostasis. In this study, researchers used bioinformatics to classify TMMs in gastric cancer single cells and investigated the biological processes and pharmacological vulnerabilities associated with different TMMs. They found that cells exhibiting non-defined TMM (NDTMM) are linked to a poorer prognosis, while NR4A1 overexpression plays a vital role in maintaining cellular homeostasis and could be a potential therapeutic target in recalcitrant gastric cancer.
Article
Oncology
Tawna L. Mangosh, Wisam N. Awadallah, Magdalena M. Grabowska, Derek J. Taylor
Summary: In AR-independent castration-resistant prostate cancer, an atypical ALT-like phenotype and elevated SLX4IP expression are observed, while AR-dependent models lack ALT hallmarks; overexpression of SLX4IP promotes an ALT-like phenotype and telomere maintenance, whereas its deficiency accelerates telomere loss and senescence.
MOLECULAR CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Nathaniel J. Robinson, Masaru Miyagi, Jessica A. Scarborough, Jacob G. Scott, Derek J. Taylor, William P. Schiemann
Summary: Telomere-associated protein SLX4IP regulates telomere proteome composition by recruiting and activating E3 SUMO ligase PIAS1 to the SLX4 complex. This activation leads to the SUMOylation of telomere-binding protein RAP1, disrupting its interaction with TRF2 and promoting its nucleocytoplasmic shuttling, ultimately activating NF-kappa B signaling and inducing Jagged-1 expression to facilitate ALT and potentially targeting ALT-driven cancers therapeutically.
Article
Cell Biology
Jiameng Dan, Zhongcheng Zhou, Fang Wang, Hua Wang, Renpeng Guo, David L. Keefe, Lin Liu
Summary: This study reveals the importance of Zscan4 in maintaining telomere length in telomerase-deficient cells. The findings demonstrate the involvement of DNA methylation and histone modifications in regulating the expression of Zscan4 and telomere maintenance.
Review
Oncology
Viola Fanfani, Martina Zatopkova, Adrian L. Harris, Francesco Pezzella, Giovanni Stracquadanio
Summary: Decades of research have shown that rare highly penetrant mutations can promote tumorigenesis, but the role of high-frequency variants in modulating cancer risk remains unclear. GWAS have linked SNPs to increased cancer risk, but the subtle effects of these mutations leave much of cancer heritability unexplained. Understanding the impact of high-frequency mutations in cancer can provide new intervention points for diagnostics, patient stratification, and treatment, particularly in prevalent malignancies like breast cancer.
SEMINARS IN CANCER BIOLOGY
(2021)
