Article
Oncology
Man Xu, Ming Sun, Xiyuan Zhang, Rosa Nguyen, Haiyan Lei, Jack F. Shern, Carol J. Thiele, Zhihui Liu
Summary: This study reveals a core transcriptional regulatory network in noradrenergic neuroblastoma, involving transcription factors PHOX2B, HAND2, GATA3, and MYCN. MYCN can bind to enhancers as well as promoters when aberrantly upregulated. HAND2 regulates chromatin accessibility and assists MYCN in enhancer invasion. Targeting both MYCN and the core regulatory factors can effectively suppress tumor growth.
Article
Oncology
Tao Liu, Lubing Gu, Zhongzhi Wu, Najah Albadari, Wei Li, Muxiang Zhou
Summary: Amplification of MYCN gene leads to overexpression of MYCN mRNA and protein, which plays a role in promoting neuroblastoma. A small molecule compound MX25-1 can bind to the 3'UTR of MYCN mRNA and induce its degradation, resulting in cell growth inhibition and cell death specifically in MYCN-amplified neuroblastoma cells. The activation of tumor suppressor miRNA let-7 is associated with the anticancer activity of MX25-1.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Samer Hanna, Riham Aly, Ghada Nour Eldeen, Alberto Adanero Velasco, Ruth Perez Alfayate
Summary: This study investigated the potential role of CHIR99021 and tideglusib as GSK-3 inhibitors in regenerative dentistry. The results showed that both small molecules were safe and effective in promoting the proliferation and maintaining the stemness of human dental pulp stem cells (hDPSCs).
Review
Cell Biology
Kiyohiro Ando, Akira Nakagawara
Summary: The RUNX family plays a crucial role in neural crest cell differentiation and may also be involved in neuroblastoma tumorigenesis. Its function in tumor development can vary depending on the specific context, including the response to chemotherapy. In primary neuroblastomas, RUNX3 acts as a tumor suppressor, while RUNX1 regulates cell proliferation in a dual manner influenced by genetic and epigenetic factors, including MYCN. This review focuses on the mechanism through which the RUNX family regulates neurotrophin receptors (Trk family) associated with neuroblastoma aggressiveness, as well as their potential involvement in functional alterations of the p53 family members in neuroblastoma tumorigenesis. Understanding the contribution of the RUNX family to neuroblastoma tumorigenesis is crucial for future molecular-based therapies.
Article
Oncology
Krista M. Dalton, Kateryna Krytska, Timothy L. Lochmann, Renata Sano, Colleen Casey, Alessia D'Aulerio, Qasim A. Khan, Giovanna Stein Crowther, Colin Coon, Jinyang Cai, Sheeba Jacob, Richard Kurupi, Bin Hu, Mikhail Dozmorov, Patricia Greninger, Andrew J. Souers, Cyril H. Benes, Yael P. Mosse, Anthony C. Faber
Summary: Venetoclax shows limited single-agent activity in MYCN-amplified neuroblastoma but can be potentiated by rational combinations with MDM2 inhibitor, MCL-1 inhibitor, or standard-of-care drugs like cyclophosphamide and topotecan. These combinations have demonstrated synergistic cell killing in preclinical models and hold promise for improving treatment efficacy in patients with amplified MYCN neuroblastoma.
MOLECULAR CANCER THERAPEUTICS
(2021)
Article
Oncology
Frank Berthold, Angela Ernst, Sandra Ackermann, Christoph Bartenhagen, Holger Christiansen, Barbara Hero, Carolina Rosswog, Dietrich von Schweinitz, Thomas Klingebiel, Irene Schmid, Thorsten Simon, Matthias Fischer
Summary: This study found that neuroblastoma patients classified as high-risk solely based on MYCN amplification generally have a more favorable outcome. However, mutations in genes of the RAS and/or p53 pathways and incomplete tumor resection are important risk factors predicting poor outcomes.
Article
Biochemistry & Molecular Biology
Anastasia E. Hains, Sakshi Uppal, John Z. Cao, Helen R. Salwen, Mark A. Applebaum, Susan L. Cohn, Lucy A. Godley
Summary: This study reveals that MYCN and HIF-1 regulate the expression of TET1 in neuroblastoma cells under hypoxia conditions, leading to an increase in 5-hydroxymethylcytosine (5-hmC) content. Gene-editing experiments confirm the role of MYCN and HIF-1 binding sites within TET1 in gene expression regulation. Bioinformatic analysis highlights the involvement of hypoxia-regulated genes, including CXCR4, in cell migration. Furthermore, cells lacking the MYCN/HIF-1 binding sites within TET1 exhibit slower migration under hypoxia, and treatment with a CXCR4 antagonist shows potential for inhibiting cell migration in MYCN-amplified neuroblastoma.
Article
Pathology
Ji Chen, Mengjiao Sun, Lei Huang, Yongjun Fang
Summary: The study showed that LINC00200 is upregulated in neuroblastoma (NB) tissues and its overexpression promotes NB cell proliferation, migration, and invasion. The possible molecular mechanism involves the binding of LINC00200 to RNA binding protein IGF2BP3 and the promotion of ZIC2 expression.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Toxicology
Majid Keshavarzi, Fatemeh Moradbeygi, Keivan Mobini, Ali Ghaffarian Bahraman, Parisa Mohammadi, Afsaneh Ghaedi, Afshin Mohammadi-Bardbori
Summary: The study found that the endogenous ligand of AhR regulates the APP gene, the interaction between AhR/WNT/CTNNB1 has a positive regulatory effect on APP mRNA and protein expression, while Notch has a negative regulatory effect, which correlates with mice's learning skills and memory.
TOXICOLOGY RESEARCH
(2022)
Article
Food Science & Technology
Karen D. Garay Buenrostro, Keila C. Ostos Mendoza, Pinal N. Kanabar, Nina S. Los, Temitope O. Lawal, Shitalben M. Patel, Alice M. Lopez, Paulina Cabada-Aguirre, Nishikant A. Raut, Mark Maienschein-Cline, Zarema Arbieva, Gail B. Mahady
Summary: This study found that combinations of vitamins A and D reduced tumor burden in mice and altered the expression of miRNAs directly associated with genes in apoptosis, tumor suppression, and epithelial-mesenchymal transition pathways. These results suggest that vitamin A and D combinations may be more effective in the treatment and prevention of cancer, as well as reducing cancer metastasis.
FUNCTIONAL FOODS IN HEALTH AND DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Claudio Asencio, Thomas Schwarzl, Sudeep Sahadevan, Matthias W. Hentze
Summary: Small noncoding RNAs play important roles in cellular and organismal biology, working with RNA-binding proteins (RBPs). In order to specifically identify RBPs binding to small noncoding RNAs, a method called small noncoding RNA interactome capture (snRIC(2C)) was developed. Through this method, nearly 300 proteins that specifically bind to RNAs smaller than 200 nt in length (snRBPs) were identified, revealing differences from the total RNA-binding proteome. Further analysis showed that most glycolytic enzymes from yeast are snRBPs, and tRNA engagement of the glycolytic enzyme GAPDH is carbon source-dependent and regulated by the RNA polymerase III repressor Maf1, suggesting a regulatory interaction between glycolysis and RNA polymerase III activity. This study demonstrates the effectiveness of snRIC(2C) and other 2C-derived methods in studying RBPs and uncovering previously unrecognized interactions.
Review
Oncology
Mary O'Reilly, Anna Linehan, Aleksandar Krstic, Walter Kolch, Kieran Sheahan, Des C. Winter, Ray Mc Dermott
Summary: Early onset colorectal cancer (EOCRC), defined as colorectal cancers in patients aged less than 50 years, is becoming an increasingly common issue globally. The incidence of EOCRC has been rising by 2% annually since 1994. Patients with EOCRC have distinct social, spiritual, fertility, and financial needs that need to be addressed. This review discusses the risk factors and management strategies for EOCRC.
Article
Multidisciplinary Sciences
Blair P. Bentley, Tomas Carrasco-Valenzuela, Elisa K. S. Ramos, Harvinder Pawar, Larissa Souza Arantes, Alana Alexander, Shreya M. Banerjee, Patrick Masterson, Martin Kuhlwilm, Martin Pippel, Jacquelyn Mountcastle, Bettina Haase, Marcela Uliano-Silva, Giulio Formenti, Kerstin Howe, William Chow, Alan Tracey, Ying Sims, Sarah Pelan, Jonathan Wood, Kelsey Yetsko, Justin R. Perrault, Kelly Stewart, Scott R. Benson, Yaniv Levy, Erica V. Todd, H. Bradley Shaffer, Peter Scott, Brian T. Henen, Robert W. Murphy, David W. Mohr, Alan F. Scott, David J. Duffy, Neil J. Gemmell, Alexander Suh, Sylke Winkler, Francoise Thibaud-Nissen, Mariana F. Nery, Tomas Marques-Bonet, Agostinho Antunes, Yaron Tikochinski, Peter H. Dutton, Olivier Fedrigo, Eugene W. Myers, Erich D. Jarvis, Camila J. Mazzoni, Lisa M. Komoroske
Summary: Sea turtles are ancient marine vertebrates that have evolved from terrestrial ancestors. Their unique physiological and ecological traits and the genomic basis behind them remain largely unknown. This study generated and analyzed high-quality reference genomes for leatherback and green turtles, revealing divergent evolution in certain gene families that may be responsible for immunological and sensory adaptations. Microchromosomes were found to play a critical role in vertebrate evolutionary adaptation. Furthermore, diversity and demographic histories differed significantly between the two species, indicating concerns over the persistence of leatherback turtles under future climate scenarios.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Joel I. Perez-Perri, Dunja Ferring-Appel, Ina Huppertz, Thomas Schwarzl, Sudeep Sahadevan, Frank Stein, Mandy Rettel, Bruno Galy, Matthias W. Hentze
Summary: The eRIC method was used to characterize the RNA-bound proteomes of three different mouse organs, revealing over 1300 active RNA-binding proteins, with nearly a quarter being previously unknown. Systematic differences in RNA binding were also observed between organs and cultured cells.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Carlos Matellan, Dariusz Lachowski, Ernesto Cortes, Kai Ning Chiam, Aleksandar Krstic, Stephen D. Thorpe, Armando E. del Rio Hernandez
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and common form of pancreatic cancer, known for its altered stromal environment and increased metastasis. Retinoids, derivatives of vitamin A, have been used in cancer treatment due to their ability to inhibit proliferation and induce cell differentiation. This study reveals that retinoic acid receptor ss (RAR-ss) can suppress the expression of myosin light chain 2 (MLC-2) in pancreatic cancer cells. MLC-2 downregulation leads to reduced cytoskeletal stiffness, impaired response to mechanical cues, and decreased invasion capacity. These findings suggest the potential of retinoids in targeting mechanical processes in pancreatic cancer.
Article
Multidisciplinary Sciences
Luis F. Iglesias-Martinez, Nora Rauch, Kieran Wynne, Brendan McCann, Walter Kolch, Jens Rauch
Summary: RAF kinases are important in cancer, particularly the BRAFV600E mutants. Although potent kinase inhibitors exist, their effects vary in different cancer types and can even induce paradoxical RAF kinase activation. Enhanced dimerization between RAF1 and BRAF contributes to both paradoxical activation and drug resistance. Mapping the interactomes of RAF1 monomers, RAF1-BRAF, and RAF1-BRAFV600E dimers, we identified and quantified over 1,000 proteins. Additionally, we analyzed the effects of vemurafenib and sorafenib, two clinically used RAF inhibitors, and found overlapping core interactomes with distinct condition-specific differences. Understanding these dynamic interactome changes may provide insights into RAF signaling and resistance mechanisms.
Article
Ecology
Liam Whitmore, Mark McCauley, Jessica A. Farrell, Maximilian R. Stammnitz, Samantha A. Koda, Narges Mashkour, Victoria Summers, Todd Osborne, Jenny Whilde, David J. Duffy
Summary: The recovery of human genomic data from environmental DNA samples raises ethical questions regarding consent, privacy, surveillance, and data ownership, which will need to be addressed as the field of environmental DNA moves forward. The field of environmental DNA (eDNA) is advancing rapidly, yet human eDNA applications remain underutilized and underconsidered. Broader adoption of eDNA analysis will bring about many well-recognized benefits, but also raises ethical dilemmas.
NATURE ECOLOGY & EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Thomas Schwarzl, Andrea Keogh, Georgina Shaw, Aleksandar Krstic, Elizabeth Clayton, Desmond G. Higgins, Walter Kolch, Frank Barry
Summary: Articular cartilage has limited regenerative capacities in humans, and tissue engineering techniques for producing hyaline cartilage are also limited. Differentiating multipotent stem cells into mature cartilage cells could be a potential solution for repairing damaged cartilage. However, chondrogenesis is a complex and inefficient process.
Article
Veterinary Sciences
Costanza Manes, Richard M. M. Herren, Annie Page, Faith D. D. Dunlap, Christopher A. A. Skibicki, Devon R. Rollinson R. Ramia, Jessica A. A. Farrell, Ilaria Capua, Raymond R. R. Carthy, David J. J. Duffy
Summary: Green turtles are affected by a tumoral disease called fibropapillomatosis (FP), characterized by the growth of tumors on various parts of their body. The tumors are categorized into rugose and smooth types, with rugose tumors growing at significantly faster rates. This study provides important preliminary data for understanding the growth-rate differences between the two tumor morphologies.
VETERINARY SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Zhi Liu, Aleksandar Krstic, Ashish Neve, Cristina Casalou, Nora Rauch, Kieran Wynne, Hilary Cassidy, Amanda McCann, Emma Kavanagh, Brendan McCann, Alfonso Blanco, Jens Rauch, Walter Kolch
Summary: KSR1 plays a critical role in mutant BRAF transformation, and its loss results in impaired cell proliferation and migration, cell cycle abnormalities, cellular senescence, and apoptosis. The study reveals that KSR1 directs ERK to phosphorylate substrates essential for cell survival, and its loss activates p38 MAPK pathway leading to cell cycle aberrations and senescence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Sudeep Sahadevan, Thileepan Sekaran, Nadia Ashaf, Marko Fritz, Matthias W. Hentze, Wolfgang Huber, Thomas Schwarzl
Summary: Transcriptome-wide detection of binding sites of RNA-binding proteins can be achieved using Individual-nucleotide crosslinking and immunoprecipitation (iCLIP) and its derivative enhanced CLIP (eCLIP) sequencing methods. The python package htseq-clip is introduced for preprocessing, extracting, and summarizing crosslink site counts from i/eCLIP experimental data. The package provides crosslink site count matrices and other metrics for filtering and downstream analyses, such as the identification of differential binding sites.
Article
Biochemistry & Molecular Biology
Thomas Schwarzl, Sudeep Sahadevan, Benjamin Lang, Milad Miladi, Rolf Backofen, Wolfgang Huber, Matthias W. Hentze, Gian Gaetano Tartaglia
Summary: Enhanced crosslinking and immunoprecipitation sequencing (eCLIP-seq) is a method for detecting RNA-binding protein binding sites. However, current analysis strategies have low replication and high false positive rates. DEWSeq, a R/Bioconductor package, improves the detection of binding regions by utilizing replicate information and size-matched input controls. It has been shown to significantly increase the number and quality of binding sites.
NUCLEIC ACIDS RESEARCH
(2023)