Article
Oncology
Shuangjie Liu, Zhuonan Liu, Chiyuan Piao, Zhe Zhang, Chuize Kong, Lei Yin, Xi Liu
Summary: The study reveals PRMT5 as a therapeutic target for bladder cancer and identifies FKA, extracted from the kava plant, as an inhibitor of PRMT5 for the treatment of bladder cancer.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Microbiology
Xiaohui Ju, Yanying Yu, Wenlin Ren, Lin Dong, Xianbin Meng, Haiteng Deng, Yuchen Nan, Qiang Ding
Summary: This study systematically analyzed the host factors in HEV replication complex using ORF1 trans-complementation system and HEV replicon. The PRMT5/WDR77 complex was found to have an inhibitory role in HEV infection among different HEV strains, but not in HCV and SARS-CoV-2 infection. The complex methylates the 458th arginine in HEV ORF1, which is responsible for HEV replication. The findings provide insights into HEV replication and viral-host interaction, and inform antiviral strategies against HEV infection.
Article
Biochemistry & Molecular Biology
Shayaan Rasheed, Renee A. Bouley, Ryan J. Yoder, Ruben C. Petreaca
Summary: Arginine methylation is an important posttranslational modification that regulates various cellular functions. PRMT5, an enzyme involved in arginine methylation, has been studied as a potential target for cancer treatment. This report analyzed PRMT5 mutations in cancer cells and identified key driver mutations that may affect the enzyme's activity and splicing, providing insights into the role of PRMT5 mutations in cancer cells and potential directions for targeted inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Shelby L. Sloan, Fiona Brown, Mackenzie Long, Christoph Weigel, Shirsha Koirala, Ji-Hyun Chung, Betsy Pray, Lynda Villagomez, Claire Hinterschied, Anuvrat Sircar, Jobeth Helmig-Mason, Alexander Prouty, Eric Brooks, Youssef Youssef, Walter Hanel, Samir Parekh, Wing Keung Chan, Zhengming Chen, Rosa Lapalombella, Lalit Sehgal, Kris Vaddi, Peggy Scherle, Selina Chen-Kiang, Maurizio Di Liberto, Olivier Elemento, Cem Meydan, Jonathan Foox, Daniel Butler, Christopher E. Mason, Robert A. Baiocchi, Lapo Alinari
Summary: Inhibition of PRMT5 in mantle cell lymphoma demonstrated antitumor activity and restored regulatory activity of the cell cycle, apoptotic cell death, and negative regulators of the B-cell receptor-PI3K/AKT signaling pathway. The selective targeting of PRMT5 shows promise as a potential therapy for patients with relapsed/refractory MCL.
Article
Cell Biology
Tian Xia, Ming Liu, Quan Zhao, Jian Ouyang, Bing Chen, Peipei Xu
Summary: PRMT5 is upregulated in multiple myeloma, and its inhibition enhances cell pyroptosis, while the expression of CASP1 negatively correlated with PRMT5 can be restored by suppressing PRMT5, promoting cell pyroptosis in MM.
CELL DEATH & DISEASE
(2021)
Article
Biotechnology & Applied Microbiology
Ying Wu, Zhe Wang, Lu Han, Zhihao Guo, Bohua Yan, Lili Guo, Huadong Zhao, Mengying Wei, Niuniu Hou, Jing Ye, Zhe Wang, Changhong Shi, Suling Liu, Ceshi Chen, Suning Chen, Ting Wang, Jun Yi, JianPing Zhou, Libo Yao, Wenxia Zhou, Rui Ling, Jian Zhang
Summary: Cancer cells regulate their response to the chemotherapeutic drug doxorubicin through RNA m6A modification. They do this by inhibiting RNA m6A modification through PRMT5 and enhancing the nuclear translocation of the demethylase ALKBH5. This leads to increased DNA repair ability and decreased efficacy of doxorubicin. The approved drug tadalafil was identified as a PRMT5 inhibitor that could enhance doxorubicin sensitivity in breast cancer cells by decreasing RNA m6A methylation.
Article
Neurosciences
David K. Dansu, Jialiang Liang, Ipek Selcen, Haiyan Zheng, Dirk F. Moore, Patrizia Casaccia
Summary: PRMT5 is an enzyme expressed in oligodendrocyte lineage cells and is responsible for methylating arginine residues on histone tails. Through mass spectrometry and iTRAQ-based proteomics, it was discovered that PRMT5 interacts with numerous proteins and is involved in various molecular functions. Additionally, PRMT5 regulates multiple cellular processes, including RNA processing, transcription, and cell migration, in oligodendrocyte progenitor cells.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Medicine, Research & Experimental
Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, Loay Kassem, Benoite Mery, Christine Lasset, Jonathan Reboulet, Isabelle Treilleux, Elisabetta Marangoni, Olivier Tredan, Muriel Le Romancer
Summary: Endocrine therapies targeting estrogen signaling have improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, resistance to treatment remains a challenge. This study identifies nuclear PRMT5 expression as a predictive marker of sensitivity to tamoxifen in breast cancer patients, and reveals the mechanism of tamoxifen stimulating ERα methylation by PRMT5. This biomarker could be used to enhance response to tamoxifen in ERα-positive breast tumors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Liu Liu, Shasha Yin, Wenjian Gan
Summary: PRMT5 is overexpressed and activated in various types of cancer, including breast cancer. This study aims to understand the mechanism of how PRMT5 is dysregulated in cancer. The results show that TRAF6-mediated ubiquitination plays a key role in the regulation of PRMT5 activity and cell proliferation. Inhibiting TRAF6 could be a potential strategy for improving PRMT5 targeted therapy.
Article
Cell Biology
Nan Wang, Tianzi Li, Wanyu Liu, Jinhua Lin, Ke Zhang, Zhenhao Li, Yanfei Huang, Yufei Shi, Meilan Xu, Xuekui Liu
Summary: PRMT5-mediated G3BP2-R468me2 enhances the binding to deubiquitinase USP7, ensuring the deubiquitination and stabilization of G3BP2. PRMT5-dependent methylation of G3BP2 is required for its deubiquitination and stabilization by USP7. The PRMT5-USP7-G3BP2 regulatory axis serves as a lipid metabolism reprogramming mechanism in tumorigenesis and could be a potential therapeutic target for head and neck squamous carcinoma.
CELL DEATH & DISEASE
(2023)
Article
Multidisciplinary Sciences
Lei Huang, Xiao-Ou Zhang, Esteban J. Rozen, Xiaomei Sun, Benjamin Sallis, Odette Verdejo-Torres, Kim Wigglesworth, Daniel Moon, Tingting Huang, John P. Cavaretta, Gang Wang, Lei Zhang, Jason M. Shohet, Mary M. Lee, Qiong Wu
Summary: The protein arginine methyltransferase 5 (PRMT5) regulates the expression of metastasis-related genes by methylating Akt protein, which is required for its phosphorylation and activation, leading to the upregulation of pro-metastatic transcription factors. Moreover, inhibiting PRMT5 can attenuate primary tumor growth and block metastasis in multiple organs, suggesting it may be a potential therapeutic target for high-risk metastatic cancers.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Charles Brobbey, Shasha Yin, Liu Liu, Lauren E. Ball, Philip H. Howe, Joe R. Delaney, Wenjian Gan
Summary: Protein arginine methyltransferase 5 (PRMT5) catalyzes methylation on arginine residues and has potential as an antitumor target. This study shows that autophagy blockage increases the sensitivity of triple negative breast cancer cells to PRMT5 inhibitor. PRMT5 mediates autophagy by methylating ULK1, and inhibition of ULK1 enhances the therapeutic effect of PRMT5 inhibitor. These findings suggest the combination of PRMT5 and autophagy inhibitors as a potential strategy in cancer therapy.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Kathleen M. Mulvaney, Christa Blomquist, Nischal Acharya, Ruitong Li, Matthew J. Ranaghan, Meghan O'Keefe, Diego J. Rodriguez, Michael J. Young, Devishi Kesar, Debjani Pal, Matthew Stokes, Alissa J. Nelson, Sidharth S. Jain, Annan Yang, Zachary Mullin-Bernstein, Josie Columbus, Fazli K. Bozal, Adam Skepner, Donald Raymond, Salvatore LaRussa, David C. McKinney, Yelena Freyzon, Yossef Baidi, Dale Porter, Andrew J. Aguirre, Alessandra Ianari, Brian McMillan, William R. Sellers
Summary: PRMT5 functions as an essential arginine methyltransferase using modular adaptor proteins with a common binding motif for substrate recruitment. Disruption of the PRMT5-substrate adaptor interface impairs the growth of MTAP-null tumor cells, making it a potential target for therapeutic inhibitors of PRMT5.
Review
Biochemistry & Molecular Biology
Soraya Epp, Shin Mei Chuah, Melinda Halasz
Summary: This review examines the intricate interplay between MYCN and known epigenetic mechanisms in neuroblastoma, and provides insights into emerging therapeutic strategies targeting these mechanisms to improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Jorg Otte, Cecilia Dyberg, Adena Pepich, John Inge Johnsen
Summary: Dysregulated expression of the transcription factor MYCN is frequently detected in nervous system tumors such as childhood neuroblastoma and is a strong predictor of poor prognosis. Increased MYCN expression is an early event in these cancers, leading to a peculiar dysregulation of cells that exhibit embryonal or cancer stem-like qualities.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Marion K. Mateos, Glenn M. Marshall, Pasquale M. Barbaro, Michael Cj Quinn, Carly George, Chelsea Mayoh, Rosemary Sutton, Tamas Revesz, Jodie E. Giles, Draga Barbaric, Frank Alvaro, Francoise Mechinaud, Daniel Catchpoole, John A. Lawson, Georgia Chenevix-Trench, Stuart MacGregor, Rishi S. Kotecha, Luciano Dalla-Pozza, Toby N. Trahair
Summary: Symptomatic methotrexate-related central neurotoxicity is a severe toxicity commonly experienced during acute lymphoblastic leukemia therapy, which can have long-term neurological complications. This study analyzed data from 1,251 Australian children and identified age and elevated serum aspartate aminotransferase as major risk factors for MTX neurotoxicity.
Article
Oncology
Danny Legge, Ling Li, Whei Moriarty, David Lee, Marianna Szemes, Asef Zahed, Leonidas Panousopoulos, Wan Yun Chung, Yara Aghabi, Jasmin Barratt, Richard Williams, Kathy Pritchard-Jones, Karim T. A. Malik, Sebastian Oltean, Keith W. Brown
Summary: The study revealed that epigenetic inactivation of ESRP2 disrupts the mesenchymal to epithelial transition in early kidney development, leading to the formation of Wilms tumour (WT). Reactivation of ESRP2 expression by DNA methyltransferase inhibition suppressed cellular proliferation in WT cell lines and inhibited tumor growth in vivo.
MOLECULAR ONCOLOGY
(2022)
Article
Cell Biology
Amanda Rush, Daniel R. Catchpoole, Georget Reaiche-Miller, Thomas Gilbert, Wayne Ng, Peter Hamilton Watson, Jennifer A. Byrne
Summary: The survey revealed that most researchers were satisfied with the biobank application processes and the suitability of received biospecimens/data, but they still preferred creating their own collections due to gaps in sample availability and to increase efficiency. Researchers mostly accessed biobanks in close proximity to them, and they often had to limit the scope of their research due to difficulties in obtaining biospecimens/data.
BIOPRESERVATION AND BIOBANKING
(2022)
Meeting Abstract
Oncology
Alexandre A. Jacome, Roberto Almeida Gil, Eduardo Dias de Moraes, Renata D'Alpino Peixoto, Jorge Alexandre Canedo, Thais Passarini, Mariana Gil, Sabrina Pereira, Larissa Amorim, Gabriel Prolla, Laura Freitas, Fernanda Coelho, Isabela Paiva, Rafael Paes, Heloisa Cruz, Matheus Costa e Silva, Carlos Gil Ferreira, Bruno Lemos Ferrari, Bernardo Garicochea, Rodrigo Dienstmann
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Immunology
Weng Hua Khoo, Katherine Jackson, Chansavath Phetsouphanh, John J. Zaunders, Jose Alquicira-Hernandez, Seyhan Yazar, Stephanie Ruiz-Diaz, Mandeep Singh, Rama Dhenni, Wunna Kyaw, Fiona Tea, Vera Merheb, Fiona X. Z. Lee, Rebecca Burrell, Annaleise Howard-Jones, Archana Koirala, Li Zhou, Aysen Yuksel, Daniel R. Catchpoole, Catherine L. Lai, Tennille L. Vitagliano, Romain Rouet, Daniel Christ, Benjamin Tang, Nicholas P. West, Shane George, John Gerrard, Peter Croucher, Anthony D. Kelleher, Christopher G. Goodnow, Jonathan D. Sprent, Joseph E. Powell, Fabienne Brilot, Ralph Nanan, Peter S. Hsu, Elissa K. Deenick, Philip N. Britton, Tri Giang Phan
Summary: Children infected with SARS-CoV-2 develop milder COVID-19 compared to adults. Analysis of T cells shows that children have a smaller immune response, with diverse naive T cells, while adults have memory T cells. This suggests that rapid clearance of the virus in children may compromise their ability to develop long-term immunity.
CLINICAL IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Evelien G. E. Hurkmans, Marije J. Klumpers, Cinzia Dello Russo, Ward De Witte, Henk-Jan Guchelaar, Hans Gelderblom, Anne-Marie Cleton-Jansen, Sita H. Vermeulen, Suzanne Kaal, Winette T. A. van der Graaf, Uta Flucke, Corrie E. M. Gidding, Hendrik W. B. Schreuder, Eveline S. J. M. de Bont, Huib N. Caron, Giovanna Gattuso, Elisabetta Schiavello, Monica Terenziani, Maura Massimino, Geoff McCowage, Sumanth Nagabushan, Anuja Limaye, Victoria Rose, Daniel Catchpoole, Andrea L. Jorgensen, Christopher Barton, Lucy Delaney, Daniel B. Hawcutt, Munir Pirmohamed, Barry Pizer, Marieke J. H. Coenen, D. Maroeska W. M. te Loo
Summary: This study aimed to identify novel genetic variants involved in platinum-induced ototoxicity. A genome-wide association study was conducted in two cohorts, and the results were combined in a meta-analysis. Variants in TSPAN5, RBBP4P5, AC010090.1, and RNU6-38P were suggestively associated with platinum-induced ototoxicity.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Chelsea Mayoh, Andrew J. Gifford, Rachael Terry, Loretta M. S. Lau, Marie Wong, Padmashree Rao, Tyler Shai-Hee, Federica Saletta, Dong-Anh Khuong-Quang, Vicky Qin, Marion K. Mateos, Deborah Meyran, Katherine E. Miller, Aysen Yuksel, Emily V. A. Mould, Rachel Bowen-James, Dinisha Govender, Akanksha Senapati, Nataliya Zhukova, Natacha Omer, Hetal Dholaria, Frank Alvaro, Heather Tapp, Yonatan Diamond, Luciano Dalla Pozza, Andrew S. Moore, Wayne Nicholls, Nicholas G. Gottardo, Geoffrey McCowage, Jordan R. Hansford, Seong-Lin Khaw, Paul J. Wood, Daniel Catchpoole, Catherine E. Cottrell, Elaine R. Mardis, Glenn M. Marshall, Vanessa Tyrrell, Michelle Haber, David S. Ziegler, Orazio Vittorio, Joseph A. Trapani, Mark J. Cowley, Paul J. Neeson, Paul G. Ekert
Summary: By combining immunohistochemistry, RNA sequencing, and whole-genome sequencing, we identified a novel 15-gene immune signature, IPASS, associated with CD8(+) T-cell infiltration in high-risk paediatric cancers. Using this signature, we estimated that up to 31% of high-risk cancers exhibit infiltrating T-cells. Furthermore, we found that PD-L1 protein expression is poorly correlated with PD-L1 RNA expression, and neoantigen load and TMB are not predictive of T-cell infiltration in paediatric cancers.
Article
Chemistry, Medicinal
Subodh Kumar Samrat, Qamar Bashir, Yiding Huang, Carl William Trieshmann, Anil Mathew Tharappel, Ran Zhang, Ke Chen, Y. Geoge Zheng, Zhong Li, Hongmin Li
Summary: This study developed a fluorescence polarization-based high throughput screening (HTS) assay to specifically target the methyltransferase (MTase) and identified two candidate drugs for the treatment of flavivirus infections.
ACS INFECTIOUS DISEASES
(2023)
Article
Chemistry, Multidisciplinary
Chng Wei Lau, Daniel Catchpoole, Simeon Simoff, Dongmo Zhang, Quang Vinh Nguyen
Summary: This paper presents a strategy that applies game theory to a decision support system for cancer treatment, using complex genomics data analytics and visualization to assist doctors in choosing treatment options and forming new treatment hypotheses.
APPLIED SCIENCES-BASEL
(2023)
Review
Biochemistry & Molecular Biology
Tyler Brown, Terry Nguyen, Bo Zhou, Y. George Zheng
Summary: Protein arginine methylation is a common post-translational modification in eukaryotic cells that affects various cellular processes. Aberrant expression and activity of protein arginine methyltransferases (PRMTs) have been observed in many diseases, including cancer. Targeting PRMTs has become an attractive therapeutic strategy. This review highlights the chemical aspects of arginine methylation and the development of chemical tools for studying PRMTs and arginine methylation in biology and disease.
RSC CHEMICAL BIOLOGY
(2023)
Article
Computer Science, Interdisciplinary Applications
Adrian Wilkins-Caruana, Madhushi Bandara, Katarzyna Musial, Daniel Catchpoole, Paul J. Kennedy
Summary: This study introduces a method called Defrag, which examines health records to infer the actual treatment steps for a particular patient group. Defrag learns the semantic and temporal meaning of healthcare event sequences, allowing it to reliably infer treatment steps from complex healthcare data. It is the first pathway-inference method to utilize a neural network, and it significantly outperforms non-NN-based methods according to tests and experiments.
JOURNAL OF BIOMEDICAL INFORMATICS
(2023)
Proceedings Paper
Computer Science, Theory & Methods
Girija Rani Karetla, Daniel Catchpoole, Paul Kennedy, Simeon Simoff, Quang Vinh Nguyen
Summary: A hybrid pipeline for analyzing, processing, and classifying RNA-Seq data, with a focus on the COVID-19 dataset, was proposed in this study. The results showed that the pipeline achieved higher accuracy compared to other methods.
PROCEEDINGS OF 2023 AUSTRALIAN COMPUTER SCIENCE WEEK, ACSW 2023
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Zhonglin Qu, Yezihalem Tegegne, Simeon J. Simoff, Paul J. Kennedy, Daniel R. Catchpoole, Quang Vinh Nguyen
Summary: UMAP is a new and effective non-linear dimensionality reduction method widely used in biomedical informatics analysis. However, its data transformation process is complex and lacks transparency. This paper compares UMAP results with PCA results using visualizations and utilizes an explainable machine learning model to optimize the input data, making UMAP and PCA processes more efficient.
DATA MINING, AUSDM 2022
(2022)
Proceedings Paper
Computer Science, Artificial Intelligence
Adrian Caruana, Madhushi Bandara, Daniel Catchpoole, Paul J. Kennedy
Summary: A meaningful understanding of clinical protocols and patient pathways using electronic health records (EHR) can improve healthcare outcomes. The novel approach CaSE outperforms traditional topic models in identifying healthcare objectives from EHR data.
AI 2021: ADVANCES IN ARTIFICIAL INTELLIGENCE
(2022)
Article
Genetics & Heredity
Aedan G. K. Roberts, Daniel R. Catchpoole, Paul J. Kennedy
Summary: There is increasing evidence that changes in gene expression variability or distribution play an important role in normal biology and diseases, especially cancer. Traditional differential expression-based analyses fail to consider genes that have difference in variability or distribution without difference in mean. In this study, a Bayesian hierarchical model was used to analyze bulk RNA-seq data and investigate differential variability and distribution in cancer. Results from analysis of tumor-normal datasets confirmed the ability of differential variability and distribution analyses to identify cancer-related genes. Additionally, it was demonstrated that differential variability analysis identifies cancer-related genes that are missed by differential expression analysis, and that differential expression and differential variability identify functionally distinct sets of potentially cancer-related genes. These findings suggest that differential variability analysis provides insights into genetic aspects of cancer that cannot be revealed by differential expression, and that differential distribution analysis allows for more comprehensive identification of cancer-related genes compared to analyses based on changes in mean or variability alone.
NAR GENOMICS AND BIOINFORMATICS
(2022)
Article
Oncology
Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu, Jana Dobrovolna, Pavel Janscak, Marcel van Vugt, Libor Macurek
Summary: Oncogene-induced replication stress is a major cause of genome instability in cancer cells. This study reveals that increased activity of PPM1D exacerbates replication stress caused by cyclin E1 overexpression, leading to abnormal cell cycle progression and accumulation of DNA copy number alterations. Pharmacological inhibition of PPM1D can alleviate replication stress-induced genome instability.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Alamelu G. Bharadwaj, Meghan E. McLean, Margaret L. Dahn, Hannah F. Cahill, Marie-Claire D. Wasson, Raj Pranap Arun, Olivia L. Walker, Brianne M. Cruickshank, Wasundara Fernando, Jaganathan Venkatesh, Penelope J. Barnes, Gillian Bethune, Gregory Knapp, Lucy K. Helyer, Carman A. Giacomantonio, David M. Waisman, Paola Marcato
Summary: ALDH1A3 regulates the plasminogen activation pathway to promote breast cancer metastasis. Co-expression of ALDH1A3 and tPA is associated with TNBC subtype, high tumor grade, and recurrent metastatic disease.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Nayela N. Chowdhury, Yi Yang, Ananya Dutta, Michelle Luo, Zimu Wei, Sara R. Abrahams, Alexey S. Revenko, Fenil Shah, Lindsey A. Miles, Robert J. Parmer, Bas de Laat, Alisa S. Wolberg, James P. Luyendyk, Melissa L. Fishel, Matthew J. Flick
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal metastatic disease associated with robust activation of the coagulation and fibrinolytic systems. Primary fibrinolytic protease plasminogen promotes PDAC tumor growth and metastatic potential through engaging plasminogen receptors on tumor cells.
MOLECULAR ONCOLOGY
(2024)
Article
Oncology
Nuria Gendrau-Sanclemente, Agnes Figueras, Kristina Gracova, Alvaro Lahiguera, Elisenda Alsina-Sanchis, Juan A. Marin-Jimenez, August Vidal, Xavier Matias-Guiu, Sergi Fernandez-Gonzalez, Marc Barahona, Lola Marti, Jordi Ponce, Francesc Vinals
Summary: High-grade serous ovarian cancer (HGSOC), the deadliest gynecological malignancy, spreads through transcoelomic dissemination. This study reveals that platelet-derived growth factor receptor beta (PDGFRβ) is essential for the formation of tumorspheres in HGSOC. Inhibition of PDGFRβ blocks the clustering of ovarian cancer cells and prevents peritoneal dissemination.
MOLECULAR ONCOLOGY
(2024)