Article
Gastroenterology & Hepatology
Hannah M. Kolev, Avital Swisa, Elisabetta Manduchi, Yemin Lan, Rachel R. Stine, Giuseppe Testa, Klaus H. Kaestner
Summary: This study investigated the role of H3K27me3 demethylation in the intestine and found that the demethylases KDM6A/B are required for the full transcriptomic and epigenomic landscape of the intestinal epithelium and the expression of key Paneth cell genes.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Aixin Hao, Yunxuan Wang, Daniel B. Stovall, Yu Wang, Guangchao Sui
Summary: Cancer therapies targeting epigenetic mechanisms, particularly involving EZH2, have shown significant progress. EZH2, a key component of PRC2, is elevated in cancers and associated with poor prognosis. In addition, studies have shown its involvement in both PRC2-dependent and independent transcriptional repression, while long non-coding RNAs have been identified as regulators of various oncogenic signaling pathways.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2021)
Article
Genetics & Heredity
Daniel Holoch, Michel Wassef, Cecilia Lovkvist, Dina Zielinski, Setareh Aflaki, Berangere Lombard, Tiphaine Hery, Damarys Loew, Martin Howard, Raphael Margueron
Summary: Epigenetic inheritance plays a role in maintaining cellular identities and transcriptional memory, particularly at Polycomb targets, depends on both histone modifications and the gene-regulatory network, varying with cellular context. Polycomb proteins are involved in regulating this type of epigenetic transcriptional memory during cell differentiation.
Article
Oncology
Stella Koutros, Nina Rao, Lee E. Moore, Michael L. Nickerson, Donghyuk Lee, Bin Zhu, Larissa A. Pardo, Dalsu Baris, Molly Schwenn, Alison Johnson, Kristine Jones, Montserrat Garcia-Closas, Ludmila Prokunina-Olsson, Debra T. Silverman, Nathaniel Rothman, Michael Dean
Summary: The study investigated the relationship between smoking and other risk factors with somatic mutations in bladder tumors. Results showed that non-silent KDM6A mutations were more common in females, and different smoking statuses were associated with specific mutational signatures. Smoking duration was found to be associated with particular mutational signatures among current and former smokers.
CLINICAL CANCER RESEARCH
(2021)
Article
Medicine, Research & Experimental
Hasibur Rehman, Darshan S. Chandrashekar, Chakravarthi Balabhadrapatruni, Saroj Nepal, Sai Akshaya Hodigere Balasubramanya, Abigail K. Shelton, Kasey R. Skinner, Ai-Hong Ma, Ting Rao, Sumit Agarwal, Marie-Lisa Eich, Alyncia D. Robinson, Gurudatta Naik, Upender Manne, George J. Netto, C. Ryan Miller, Chong-Xian Pan, Guru Sonpavde, Sooryanarayana Varambally, James E. Ferguson
Summary: The study reveals that bladder cancers with ARID1A mutations are more sensitive to EZH2 inhibitors and/or PI3K inhibitors. Mechanistic studies demonstrate that ARID1A deficiency leads to a dependency on PI3K signaling, and EZH2 inhibitor sensitivity is associated with upregulation of PIK3IP1. Moreover, combination therapy with EZH2 and PI3K inhibitors shows a synergistic effect on ARID1A-deficient bladder cancer.
Article
Multidisciplinary Sciences
Hany A. Abdel-Hafiz, Saravana Kumar Kailasam Mani, Wesley Huang, I. I. I. Kenneth H. Gouin, Yuzhou Chang, Tong Xiao, Qin Ma, Zihai Li, Simon R. V. Knott, Dan Theodorescu
Summary: In this study, single-cell RNA sequencing was used to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. Proportional and gene expression differences were found in epithelial and non-epithelial subpopulations between male and female tumors. Several genes were found to predict sex-specific survival in human BLCA datasets. Novel and clinically relevant sex-specific transcriptional signatures were identified, including immune cells in the tumor microenvironment. It validated the relevance of the BBN model for studying sex differences in human BLCA.
Article
Gastroenterology & Hepatology
Lei Ren, Hong Deng, Yu Jiang, Chunfeng Liu
Summary: This study investigates the dual regulation of EZH2 and KDM6A in the upstream modulation of SALL4, promoting GC cell progression via the Wnt/beta-catenin pathway. The results show that SALL4 is upregulated in GC cells and regulates the progression and invasion of GC cells through the Wnt/beta-catenin pathway, which can be separately upregulated or downregulated by KDM6A or EZH2.
DIGESTIVE DISEASES AND SCIENCES
(2023)
Article
Oncology
Sehbanul Islam, Parul Dutta, Osheen Sahay, Kesavaperumal Gopalakrishnan, Sushrita Roy Muhury, Parinitha Parameshwar, Praveenkumar Shetty, Manas Kumar Santra
Summary: The oncogene c-Myc suppresses the expression of FBXO31 in ovarian cancer, impairing its tumor-suppressive functions. In contrast, FBXO31 degrades c-Myc through the proteasome pathway, inhibiting ovarian cancer growth. The c-Myc-FBXO31 axis shows promise as a target for developing better cancer therapies.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Medicine, Research & Experimental
Tao Liu, Yu Yang, Zhe Xie, Qingya Luo, Dan Yang, Xiaoyi Liu, Hongyan Zhao, Qinglv Wei, Yi Liu, Lanfang Li, Yuya Wang, Fang Wang, Jianhua Yu, Jing Xu, Jia Yu, Ping Yi
Summary: RBPs, particularly QKI5, play a tumor-suppressive role in ovarian cancer by negatively regulating the expression of TAZ and its downstream targets, such as CTGF and CYR61. QKI5 can inhibit the growth and metastasis of OC cells in vitro and in vivo, indicating its potential as a therapeutic target for OC.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Biochemistry & Molecular Biology
Ngai Ting Chan, Junfeng Huang, Gui Ma, Hao Zeng, Kristine Donahue, Yidan Wang, Lingjun Li, Wei Xu
Summary: CTR9 is a scaffold subunit in PAFc complex and plays a crucial role in controlling H3K27me3 levels and genomic distribution mediated by PRC2. Loss of CTR9 leads to increased H3K27me3 levels, expanded recruitment of PRC2 on chromatin, and a shift from less active PRC2.2 to more active PRC2.1, resulting in hypersensitivity of breast cancer cells to PRC2 inhibitors.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Neurosciences
Serena Buontempo, Pasquale Laise, James M. Hughes, Sebastiano Trattaro, Vivek Das, Chantal Rencurel, Giuseppe Testa
Summary: This study reveals the role of EZH2-mediated H3K27me3 in neuronal differentiation. Using a mouse model and transcriptomic analysis, it was found that the loss of EZH2 leads to dysregulation of transcriptional circuitries related to neuronal differentiation and synaptic plasticity, as well as the expression of GABAergic genes during glutamatergic neuron differentiation.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Cell Biology
Alexandre Videira, Felipe C. Beckedorff, Lucas F. daSilva, Sergio Verjovski-Almeida
Summary: The study has shown that PVT1 is involved in signaling a genome-wide androgen-dependent transcriptional repressive program of tumor suppressor genes in prostate cancer cells. The transcriptional inhibition of tumor suppressor genes by PVT1 highlights the pathway to investigating the oncogenic role of PVT1 in cancer.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Multidisciplinary Sciences
Tsz-Yin Chan, Christina M. Egbert, Julia E. Maxson, Adam Siddiqui, Logan J. Larsen, Kristina Kohler, Eranga Roshan Balasooriya, Katie L. Pennington, Tsz-Ming Tsang, Madison Frey, Erik J. Soderblom, Huimin Geng, Markus Muschen, Tetyana V. Forostyan, Savannah Free, Gaelle Mercenne, Courtney J. Banks, Jonard Valdoz, Clifford J. Whatcott, Jason M. Foulks, David J. Bearss, Thomas O'Hare, David C. S. Huang, Kenneth A. Christensen, James Moody, Steven L. Warner, Jeffrey W. Tyner, Joshua L. Andersen
Summary: TNK1, a non-receptor tyrosine kinase, has been found to play a key role in cancer by toggling between inactive states involving interaction with 14-3-3 and active states through ubiquitin binding. The discovery of a TNK1 inhibitor, TP-5801, highlights its potential as a therapeutic target for TNK1-transformed cells and tumor growth suppression in vivo.
NATURE COMMUNICATIONS
(2021)
Review
Pathology
Hesham A. El-Mahdy, Elsayed G. E. Elsakka, Ahmed A. El-Husseiny, Ahmed Ismail, Amr Mohamed Yehia, Nourhan M. Abdelmaksoud, Reham A. A. Elshimy, Mina Noshy, Ahmed S. Doghish
Summary: Bladder cancer is the 11th most popular cancer in females and 4th in males. Efforts have been made to improve BC patients' care, and new approaches have been developed to enhance the efficiency of BC diagnosis, prognosis, therapeutics, and monitoring.
PATHOLOGY RESEARCH AND PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Jiangshu He, Jin Yang, Lin Chen, Pinglin He, Xun Liu, Kai Wang, Taotao Dong, Jia Li, Xudong Ma, Amend Bastian, Stenzl Arnulf
Summary: Bladder outlet obstruction (BOO) is a chronic disease caused by benign prostatic hyperplasia. This study explored the role of serum/glucocorticoid-regulated kinase 1 (SGK1) and activated T cell nuclear factor transcription factor 2 (NFAT2) in the proliferation of bladder smooth muscle cells in mouse BOO. It was found that SGK1 targeted TRPV1 to regulate the proliferation of smooth muscle cells and affect bladder remodeling after BOO.
Letter
Multidisciplinary Sciences
Jing Quan Lim, Soon Thye Lim, Choon Kiat Ong
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Katti Arroyo, Anahit Nargizyan, Francianne G. Andrade, Swe Swe Myint, Sabrina Lu, Priyatama Pandey, Amy Yee, Adam J. de Smith, Joseph L. Wiemels
Summary: This study compared the performance of ddPCR and NGS for DNA methylation detection. The results showed that ddPCR has better high-throughput capacity and specificity in large-scale population studies.
Article
Hematology
Qianxi Feng, Mi Zhou, Shaobo Li, Libby Morimoto, Helen Hansen, Swe Swe Myint, Rong Wang, Catherine Metayer, Alice Kang, Anna Lisa Fear, Derek Pappas, Henry Erlich, Jill A. Hollenbach, Nicholas Mancuso, Elizabeth Trachtenberg, Adam J. de Smith, Xiaomei Ma, Joseph L. Wiemels
Summary: This study explores the relationship between childhood acute lymphoblastic leukemia (ALL) and the interaction between maternal-fetal immune receptors, finding different associations between different ethnic groups. The study also reveals associations between activating profiles and immune factors related to cytokine control, without demonstrating a causal mediation of cytokines on ALL risk.
Letter
Hematology
Shaobo Li, Pagna Sok, Keren Xu, Ivo S. Muskens, Natalina Elliott, Swe Swe Myint, Priyatama Pandey, Helen M. Hansen, Libby M. Morimoto, Alice Y. Kang, Catherine Metayer, Xiaomei Ma, Beth A. Mueller, Anindita Roy, Irene Roberts, Karen R. Rabin, Austin L. Brown, Philip J. Lupo, Joseph L. Wiemels, Adam J. de Smith
Article
Cell Biology
Keren Xu, Shaobo Li, Ivo S. Muskens, Natalina Elliott, Swe Swe Myint, Priyatama Pandey, Helen M. Hansen, Libby M. Morimoto, Alice Y. Kang, Xiaomei Ma, Catherine Metayer, Beth A. Mueller, Irene Roberts, Kyle M. Walsh, Steve Horvath, Joseph L. Wiemels, Adam J. Smith
Summary: The study revealed that accelerated epigenetic aging in the blood of Down syndrome (DS) patients begins prenatally and is associated with somatic GATA1 mutations. DS newborns showed a significant increase in DNAmSkinBloodClock, but were not associated with epigenetic gestational age acceleration.
Article
Hematology
Jing Quan Lim, Dachuan Huang, Jason Yongsheng Chan, Yurike Laurensia, Esther Kam Yin Wong, Daryl Ming Zhe Cheah, Burton Kuan Hui Chia, Wen-Yu Chuang, Ming-Chung Kuo, Yi-Jiun Su, Qing-qing Cai, Yanfen Feng, Huilan Rao, Li-Na Feng, Pan-Pan Wei, Jie-Rong Chen, Bo-Wei Han, Guo-Wang Lin, Jun Cai, Yu Fang, Jing Tan, Huangming Hong, Yanhui Liu, Fen Zhang, Wenyu Li, Michelle L. M. Poon, Siok-Bian Ng, Anand Jeyasekharan, Jeslin Chian Hung Ha, Lay Poh Khoo, Suk Teng Chin, Wan Lu Pang, Rebecca Kee, Chee Leong Cheng, Nicholas Francis Grigoropoulos, Tiffany Tang, Miriam Tao, Mohamad Farid, Kia Joo Puan, Jie Xiong, Wei-Li Zhao, Chiea Chuen Khor, William Hwang, Won Seog Kim, Elias Campo, Patrick Tan, Bin Tean Teh, Wee-Joo Chng, Olaf Rotzschke, Thomas Tousseyn, Hui-Qiang Huang, Steve Rozen, Soon Thye Lim, Lee-Yung Shih, Jin-Xin Bei, Choon Kiat Ong
Summary: We developed a genomic prognostic model (GPM) for Natural-killer/T cell lymphoma (NKTCL) using next-generation sequencing. The GPM, based on the mutational status of 13 prognostic genes, showed significant correlation with known risk-features and improved prognostication for both progression-free survival (PFS) and overall survival (OS) in NKTCL patients.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Respiratory System
Hui Fang Lim, Nadia Suray Tan, Roghayeh Dehghan, Meixin Shen, Mei Fong Liew, Stella Wei Lee Bee, Yee Yen Sia, Jianjun Liu, Chiea Chuen Khor, Immanuel Kwok, Lai Guan Ng, Veronique Angeli, Rajkumar Dorajoo
Summary: This study found that telomere length in sputum of bronchiectasis patients is significantly shortened, and identified the signaling pathways and genes related to telomere shortening.
Article
Immunology
Elisa Montaldo, Eleonora Lusito, Valentina Bianchessi, Nicoletta Caronni, Serena Scala, Luca Basso-Ricci, Carla Cantaffa, Alice Masserdotti, Mattia Barilaro, Simona Barresi, Marco Genua, Francesco Maria Vittoria, Giulia Barbiera, Dejan Lazarevic, Carlo Messina, Elisabetta Xue, Sarah Marktel, Cristina Tresoldi, Raffaella Milani, Paola Ronchi, Salvatore Gattillo, Luca Santoleri, Raffaella Di Micco, Andrea Ditadi, Giulio Belfiori, Francesca Aleotti, Matteo Maria Naldini, Bernhard Gentner, Elisa Gardiman, Nicola Tamassia, Marco Antonio Cassatella, Andres Hidalgo, Immanuel Kwok, Lai Guan Ng, Stefano Crippa, Massimo Falconi, Francesca Pettinella, Patrizia Scapini, Luigi Naldini, Fabio Ciceri, Alessandro Aiuti, Renato Ostuni
Summary: Recent studies have found that human neutrophils exhibit substantial function diversity. This study performs immunophenotyping and transcriptome analysis to characterize the heterogeneity of human neutrophils under steady state and stress-induced conditions. The researchers uncover an extreme diversity of human neutrophils in vivo, reflecting the rates of cell mobilization, differentiation, and exposure to environmental signals. The findings suggest that systematic characterization of neutrophil plasticity may lead to the discovery of clinically relevant biomarkers and the development of diagnostic and therapeutic tools.
Article
Multidisciplinary Sciences
Eric M. Nickels, Shaobo Li, Swe Swe Myint, Katti Arroyo, Qianxi Feng, Kimberly D. Siegmund, Adam J. de Smith, Joseph L. Wiemels
Summary: The study examines the role of DNA methylation variation in predisposing to pediatric acute lymphoblastic leukemia using a discordant twin model. The findings suggest that DNA hypomethylation may contribute to the risk of leukemia development.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Shaobo Li, Charleston W. K. Chiang, Swe Swe Myint, Katti Arroyo, Tsz Fung Chan, Libby Morimoto, Catherine Metayer, Adam J. de Smith, Kyle M. Walsh, Joseph L. Wiemels
Summary: This study found a higher proportion of global European ancestry in PA cases compared to the control group of Latino ethnicity. Admixture mapping analysis identified several genomic loci associated with PA risk. Further fine mapping analysis revealed several potential genetic loci contributing to childhood PA risk.
Article
Genetics & Heredity
Eleanor Wong, Nicolas Bertin, Maxime Hebrard, Roberto Tirado-Magallanes, Claire Bellis, Weng Khong Lim, Chee Yong Chua, Philomena Mei Lin Tong, Raymond Chua, Kenneth Mak, Tit Meng Lim, Wei Yang Cheong, Kwee Eng Thien, Khean Teik Goh, Jin-Fang Chai, Jimmy Lee, Joseph Jao-Yiu Sung, Tien Yin Wong, Calvin Woon Loong D. Chin, Peter Gluckman, Liuh Ling Goh, Kenneth Hon Kim Ban, Tin Wee M. Tan, Rob M. Van Dam, Yik Ying Teo, Marie Loh, Paul Eillot, Eng Sing Lee, Joanne Ngeow, Elio Riboli, Rinkoo Dalan, Irfahan Kassam, Lakshmi Narayanan Lakshmanan, Tock Han Lim, Hong Kiat Ng, Theresia Mina, Darwin Tay, Charumathi Sabanayagam, Yih Chung Tham, Tyler Rim, Tin Aung, Miao Ling Chee, Hengtong Li, Miao Li Chee, Khung Keong Yeo, Stuart Alexander Cook, Chee Jian Pua, Chengxi Yang, Yap Seng Chong, Johan Gunnar Eriksson, Kok Hian Tan, Fabian Yap, Chia Wei Lim, Pi Kuang Tsai, Wen Jie Chew, Wey Ching Sim, Li-xian Grace Toh, Clarabelle Bitong Lin, Yee Yen Sia, Tat Hung Koh, Wee Yang Meah, Joanna Hui Juan Tan, Justin Jeyakani, Jack Ow, Shimin Ang, Ashar J. Malik, Dimitar Kenanov, Xueling Sim, Ching-Yu Cheng, Sonia Davila, Neerja Karnani, Khai Pang Leong, Jianjun Liu, Shyam Prabhakar, Sebastian Maurer-Stroh, Chandra Shekhar Verma, Pavitra Krishnaswamy, Rick Siow Mong Goh, Irenaeus Chia, Clarissa Ho, Doreen Low, Suchin Virabhak, Jacklyn Yong, Weiling Zheng, Shih Wee Seow, Yee Kwang Seck, Mingshi Koh, John C. Chambers, E. Shyong Tai, Patrick Tan
Summary: This article discusses Singapore's efforts to establish a National Precision Medicine Strategy by integrating genomic, clinical, and lifestyle data of up to one million individuals. Precision medicine has the potential to revolutionize healthcare by detecting diseases early, refining diagnoses, and tailoring treatments for groups and individuals. The lack of representation of Asian ancestries in existing genomic-phenotypic databases presents a missed opportunity for new discoveries, especially for diseases relevant to these populations. The Singapore National Precision Medicine initiative aims to generate integrated data from various sources over a 10-year period, including genomic, lifestyle, health, social, and environmental data, in order to promote precision medicine adoption and address social, ethical, legal, and regulatory challenges.
Article
Biochemistry & Molecular Biology
Marc Thibonnier, Sujoy Ghosh
Summary: We propose an innovative approach to drug research and development for miRNA oligonucleotide therapeutics. This model involves collaboration between a biotechnology company, AptamiR Therapeutics, and Centers of Excellence in Academic Institutions. Our focus is on developing safe, effective, and convenient miRNA ONT agents for metabolic disorders and ovarian cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Vetrivel Sengottuvel, Monalisa Hota, Jeongah Oh, Dwight L. Galam, Bernice H. Wong, Markus R. Wenk, Sujoy Ghosh, Federico Torta, David L. Silver
Summary: Patients with autosomal recessive microcephaly 15 caused by deficiency in Mfsd2a, a transporter for LPC in oligodendrocytes, exhibit both microcephaly and hypomyelination. Mfsd2a is specifically expressed in oligodendrocyte precursor cells (OPCs) and plays a critical role in OPC development. Loss of Mfsd2a leads to precocious differentiation of OPCs into immature oligodendrocytes and impaired maturation into myelinating oligodendrocytes, resulting in postnatal brain hypomyelination.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Shaobo Li, Xiaowu Gai, Swe Swe Myint, Katti Arroyo, Libby Morimoto, Catherine Metayer, Adam J. de Smith, Kyle M. Walsh, Joseph L. Wiemels
Summary: This study identifies a potential role of functional mitochondrial ribosomal RNA variant in childhood glioblastoma risk and suggests the involvement of both mitochondrial and nuclear-mitochondrial DNA polymorphisms in GBM tumorigenesis.
NEURO-ONCOLOGY ADVANCES
(2022)
Article
Cell Biology
Josephine Hendrikson, Ying Liu, Wai Har Ng, Jing Yi Lee, Abner Herbert Lim, Jui Wan Loh, Cedric C. Y. Ng, Whee Sze Ong, Joey Wee-Shan Tan, Qiu Xuan Tan, Gillian Ng, Nicholas B. Shannon, Weng Khong Lim, Tony K. H. Lim, Clarinda Chua, Jolene Si Min Wong, Grace Hwei Ching Tan, Jimmy Bok Yan So, Khay Guan Yeoh, Bin Tean Teh, Claramae Shulyn Chia, Khee Chee Soo, Oi Lian Kon, Iain Beehuat Tan, Jason Yongsheng Chan, Melissa Ching Ching Teo, Chin-Ann J. Ong
Summary: This study demonstrates the importance of the STAT3 signaling pathway in peritoneal carcinomatosis and identifies potential activating ligands. The study also validates the prognostic biomarker panel, including PAI-1, and highlights a therapeutic opportunity based on paracrine addiction.
CELL REPORTS MEDICINE
(2022)