Article
Cell Biology
Yuchao Diao, Yingwei Li, Zixiang Wang, Shourong Wang, Peng Li, Beihua Kong
Summary: Studies have shown that overexpression of SF3B4 in ovarian cancer patients is associated with poor prognosis, and miR-509-3p negatively regulates SF3B4 expression which in turn promotes ovarian cancer progression. Additionally, SF3B4's splicing of RAD52 also impacts the development of ovarian cancer.
CELL DEATH & DISEASE
(2022)
Review
Genetics & Heredity
Renfu Shang, Seungjae Lee, Gayan Senavirathne, Eric C. Lai
Summary: In this Review, the authors discuss how new technologies have advanced our understanding of miRNA biology. They provide an overview of miRNA biogenesis, function, and processing, and highlight the challenges for future research.
NATURE REVIEWS GENETICS
(2023)
Article
Microbiology
Giraldina Trevejo-Nunez, Becky Lin, Li Fan, Felix E. Y. Aggor, Partha S. Biswas, Kong Chen, Sarah L. Gaffen
Summary: Excessive inflammation can cause tissue damage and autoimmunity. Reg1 deficiency exacerbates autoimmune diseases but confers resistance to Klebsiella pneumoniae (KP) by affecting type I interferon regulation.
Review
Cell Biology
Junhong Chen, Jie Gu, Mengtian Tang, Zhiqiang Liao, Rui Tang, Lianqing Zhou, Min Su, Jiarui Jiang, Yingbin Hu, Yongyi Chen, Yujuan Zhou, Qianjin Liao, Wei Xiong, Jumei Zhou, Yanyan Tang, Shaolin Nie
Summary: circRNAs are closed back-splicing products of precursor mRNA with stable expression and unique structure in eukaryotes. They play essential biological roles in tumors through various regulatory mechanisms, such as biogenesis regulation by RNA-binding proteins. Furthermore, circRNAs can act as protein sponges, be translated themselves, or regulate posttranslational modifications of proteins, revealing potential interactions with functional proteins in cancer and uncovering unknown regulatory mechanisms.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sukhleen Kour, Tyler Fortuna, Eric N. Anderson, Darilang Mawrie, Jessica Bilstein, Ramakrishnan Sivasubramanian, Caroline Ward, Rishit Roy, Dhivyaa Rajasundaram, Jared Sterneckert, Udai Bhan Pandey
Summary: This research discovers that Drosha and two Drosha-dependent microRNAs have regulatory effects on the expression of FUS and prevent its cytoplasmic segregation. Depletion of Drosha can alleviate FUS-mediated degeneration and motor defects. miR-378i and miR-6832-5p differentially regulate the expression, solubility, and cytoplasmic aggregation of FUS.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Cell Biology
Yolanda Martin-Martin, Ana Perez-Garcia, Marta Torrecilla-Parra, Mario Fernandez-de Frutos, Virginia Pardo-Marques, Maria Jose Casarejos, Rebeca Busto, Cristina M. Ramirez
Summary: IDE is implicated in the relation between AD, T2DM, and hyperinsulinemia. The regulation of IDE expression is not well understood, but recent research indicates that miR-7, miR-125, miR-490, and miR-199, as well as RNA binding proteins, may play a role in post-transcriptional regulation of IDE. These findings suggest potential therapeutic targets for metabolic diseases including AD and T2DM.
Article
Biochemical Research Methods
Lei Xu, Shanshan Jiang, Jin Wu, Quan Zou
Summary: Exploring the function of proteins in protein-nucleic acid interactions is important for understanding related biological events and predicting these interactions. Establishing databases by collecting and identifying protein sequence information helps in predicting protein function, leading to improved prediction accuracy.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Oncology
Qi Zheng, Wei Hou
Summary: MicroRNAs (miRs) are small non-coding RNA molecules that play key roles in regulating gene expression and cellular functions, particularly in angiogenesis related to tumor development and progression. Investigating the roles of miRs in angiogenesis may lead to novel strategies for treating tumors, and their potential as biomarkers for diagnosing and monitoring therapy response is also being explored.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Chemistry, Multidisciplinary
Xu Zhou, Ramkrishna Mitra, Fei Hou, Shunheng Zhou, Lihong Wang, Wei Jiang
Summary: Adenosine-to-inosine RNA editing plays a critical role in cancer therapy response. A comprehensive identification of drug resistance-related RNA editing events and understanding of their mechanism is lacking. This study identifies 7157 differential editing sites (DESs) from 98,127 informative RNA editing sites in tumor tissues and reveals various editing patterns in resistant samples. RNA-binding proteins are found to potentially regulate these editing events. DESs are significantly enriched in 3'-UTRs and their impact on miRNA regulations is explored. Genes associated with DESs are involved in drug resistance-related functions. A convenient online resource for retrieving DESs is built. These findings provide insights into the landscape and regulatory mechanism of RNA editing in drug resistance and offer new therapeutic targets for reversing drug resistance.
Article
Multidisciplinary Sciences
Dan Song, Lisha Kuang, Lin Yang, Lei Wang, Hao Li, Xiu Li, Zhimin Zhu, Chaowei Shi, Haining Zhu, Weimin Gong
Summary: The study reveals the mechanism of stress granule (SGs) formation, demonstrating the interaction of G3BP1 protein with Caprin-1 and USP10 to facilitate or suppress SG formation. The N- and C-terminal domains of Caprin-1 play opposing roles in regulating SG formation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Patricia Gonzalez-Rodriguez, Daniel J. Klionsky, Bertrand Joseph
Summary: This article reviews the regulatory role of RNA alternative splicing in autophagy and its relevance to diseases. It also discusses the therapeutic strategies of targeting alternative splicing and autophagy as well as selectively regulating autophagy-related protein isoforms.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Peter Gollwitzer, Nina Gruetzmacher, Sabine Wilhelm, Daniel Kuemmel, Constantinos Demetriades
Summary: Amino acid availability controls mTORC1 activity through a Rag GTPase complex, with RagD playing a specific role in recruiting mTORC1 to lysosomes and promoting phosphorylation of lysosomal substrates, while both RagC and RagA are involved in the phosphorylation of non-lysosomal substrates.
NATURE CELL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Bernhard Dumoulin, Christoph Ufer, Hartmut Kuhn, Sajad Sofi
Summary: GRSF1, a widely distributed RNA-binding protein in eukaryotic cells, is involved in various physiological processes and the pathogenesis of diseases.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Anna Di Matteo, Elisa Belloni, Davide Pradella, Anna Maria Chiaravalli, Giacomo Maria Pini, Mattia Bugatti, Roberta Alfieri, Chiara Barzan, Elena Franganillo Tena, Silvia Bione, Elisa Terenzani, Fausto Sessa, Christopher D. R. Wyatt, William Vermi, Claudia Ghigna
Summary: Angiogenesis is crucial for cancer progression, but current anti-angiogenic drugs have limited clinical benefits. This study provides a deeper understanding of the mechanisms regulating tumor vessel growth and identifies NOVA2 as a critical regulator of angiogenesis and vascular development. Moreover, the upregulation of NOVA2 in gastric cancer endothelial cells is associated with poor patient outcome, suggesting its potential as a biomarker and therapeutic target for anti-angiogenic treatment of gastric cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Neurosciences
Jonathan G. Hanley
Summary: AMPA receptors play a critical role in synaptic transmission and brain function, with their expression at synapses determining functional connectivity of neuronal circuits and underpinning learning and memory. Dysregulation of excitatory synaptic transmission and plasticity processes is involved in various neurological disorders. MiRNAs play a role in regulating AMPAR subunit expression and synaptic plasticity, potentially contributing to both physiological and pathological changes in the brain.
Review
Hematology
Eric Engelbrecht, Calum A. MacRae, Timothy Hla
Summary: Membrane phospholipid metabolism produces lysophospholipids, which act as ligands for G-protein-coupled receptors influencing various biological processes. Lysophosphatidic acid and S1P are particularly significant in vascular development and cardiovascular diseases, with potential connections to the Wnt pathway. These findings highlight the importance of lysophospholipid signaling in cardiovascular disease and the potential for novel therapeutic strategies.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Anja Nitzsche, Marine Poittevin, Ammar Benarab, Philippe Bonnin, Giuseppe Faraco, Hiroki Uchida, Julie Favre, Lidia Garcia-Bonilla, Manuela C. L. Garcia, Pierre-Louis Leger, Patrice Therond, Thomas Mathivet, Gwennhael Autret, Veronique Baudrie, Ludovic Couty, Mari Kono, Aline Chevallier, Hira Niazi, Pierre-Louis Tharaux, Jerold Chun, Susan R. Schwab, Anne Eichmann, Bertrand Tavitian, Richard L. Proia, Christiane Charriaut-Marlangue, Teresa Sanchez, Nathalie Kubis, Daniel Henrion, Costantino Iadecola, Timothy Hla, Eric Camerer
Summary: This study explores the role of endothelial cell S1P(1) in the naive and ischemic brain as a potential target for cerebrovascular therapy. Endothelial S1P(1) plays a critical vascular protective role in the mouse brain, sustaining endothelial functions and expanding during ischemia. Disruption of this pathway exacerbates brain injury in ischemic stroke models, highlighting the importance of S1P signaling in maintaining perfusion and microvascular patency in the ischemic penumbra.
CIRCULATION RESEARCH
(2021)
Letter
Multidisciplinary Sciences
Timothy Hla
Letter
Multidisciplinary Sciences
Jianping Li, Xiaoqian Zhu, Dengsheng Wu
Article
Biochemistry & Molecular Biology
De Yu Mao, Matthew L. Kleinjan, Irina Jilishitz, Bhairavi Swaminathan, Hideru Obinata, Yulia A. Komarova, Kayla J. Bayless, Timothy Hla, Jan K. Kitajewski
Summary: CLIC1 and CLIC4 play crucial roles in regulating GPCR pathways associated with vascular development and disease in endothelial cells. They translocate to the plasma membrane in response to S1P and mediate the activation of small GTPases downstream of S1PR1 and S1PR2/3, respectively. These CLIC-mediated mechanisms are essential for S1P-induced stimulation of barrier function in endothelial cell monolayers.
Article
Biochemistry & Molecular Biology
Rachel S. Knipe, Jillian J. Spinney, Elizabeth A. Abe, Clemens K. Probst, Alicia Franklin, Amanda Logue, Francesca Giacona, Matt Drummond, Jason Griffith, Patricia L. Brazee, Lida P. Hariri, Sydney B. Montesi, Katherine E. Black, Timothy Hla, Andrew Kuo, Andreane Cartier, Eric Engelbrecht, Christina Christoffersen, Barry S. Shea, Andrew M. Tager, Benjamin D. Medoff
Summary: Idiopathic pulmonary fibrosis is a chronic disease that causes respiratory failure. This study reveals the importance of vascular permeability in lung repair and fibrosis following injury, and the potential role of lipid mediator S1P in regulating this process.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Review
Pathology
Kuniyuki Kano, Junken Aoki, Timothy Hla
Summary: Lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are important extracellular lipid mediators that signal through specific G protein-coupled receptors. They play crucial roles in various biological processes and diseases, including cellular stress signaling, inflammation, and host defense responses. LPA is involved in regulating fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and neuroectodermal developmental disorders, while S1P controls collective behavior, apoptotic cell clearance, and immunesurveillance of cancers. The study of lysophospholipids has led to the development of new therapeutics for autoimmune diseases and holds promise for future treatments of fibrotic disorders, vascular diseases, and cancer.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2022)
Article
Surgery
Lawrence N. Diebel, David M. Liberati, Timothy Hla, Steven Swendeman
Summary: The study found that carrier-based sphingosine 1-phosphate may have a protective effect in early hemorrhagic shock resuscitation, with apolipoprotein M+ sphingosine 1-phosphate showing the most significant effect.
Article
Hematology
Pascal Yazbeck, Xavier Cullere, Paul Bennett, Vijay Yajnik, Huan Wang, Kenji Kawada, Vanessa M. Davis, Asit Parikh, Andrew Kuo, Vijayashree Mysore, Timothy Hla, David S. Milstone, Tanya N. Mayadas
Summary: The study reveals that DOCK4, an atypical Rho family GTPase GEF, plays a critical role in lung vascular barrier function by regulating AJs. DOCK4 deficiency leads to lung hemorrhage, increased microvascular permeability, and impaired response to S1P-induced permeability changes. Additionally, S1P may act as a potential upstream regulator of DOCK4 activity.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Retraction
Oncology
Kotha Subbaramaiah, Louise R. Howe, Priya Bhardwaj, Baoheng Du, Claudia Gravaghi, Rhonda K. Yantiss, Xi Kathy Zhou, Victoria A. Blaho, Timothy Hla, Peiying Yang, Levy Kopelovich, Clifford A. Hudis, Andrew J. Dannenberg
CANCER PREVENTION RESEARCH
(2022)
Review
Rheumatology
Nathalie Burg, Jane E. Salmon, Timothy Hla
Summary: Sphingosine 1-phosphate plays essential roles in autoimmune rheumatic diseases, and modulating its signaling may offer potential therapeutic approaches. Understanding the S1P-S1PR signaling axis could provide novel insights into the treatment of systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis.
NATURE REVIEWS RHEUMATOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Xulai Shia, Wanshan Wang, Jia Li, Ting Wang, Yan Lin, Siqi Huang, Aarti Kuver, Chengshui Chen, Timothy Hla, Xi Li, Kezhi Dai
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Medicine, Research & Experimental
Michel Levesque, Timothy Hla
Summary: S1P and its receptors (S1PRs) play important roles in vascular development, homeostasis, and diseases as well-studied examples of GPCR signaling axis. The rapid biochemical cascades involved in S1P signaling are well understood, but the gene-expression regulation by S1PRs is less clear. This review focuses on how S1PRs regulate nuclear chromatin changes and gene transcription to modulate vascular and lymphatic endothelial phenotypic changes during embryonic development and adult homeostasis. These findings are crucial for understanding stimulus-evoked gene regulation in the vascular endothelium and developing therapeutic drugs for autoimmune and vascular diseases, considering the adverse events caused by S1PR-targeted drugs.
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
(2023)
Article
Biology
Andrew Kuo, Antonio Checa, Colin Niaudet, Bongnam Jung, Zhongjie Fu, Craig E. Wheelock, Sasha A. Singh, Masanori Aikawa, Lois E. Smith, Richard L. Proia, Timothy Hla
Summary: This study reveals the crucial role of endothelial sphingolipid biosynthesis in regulating vascular development, maintaining circulatory and peripheral organ sphingolipid levels, and contributing to lipid raft formation and efficient signaling. The deletion of SPTLC1 in endothelial cells leads to impaired proliferation, differentiation, and delayed retinal vascular development. Furthermore, EC-derived sphingolipid metabolites are in constant flux between the vasculature, circulation, and non-CNS organs, and play a role in hepatocyte response to stress.
Article
Medicine, Research & Experimental
Colin Niaudet, Bongnam Jung, Andrew Kuo, Steven Swendeman, Edward Bull, Takahiro Seno, Reed Crocker, Zhongjie Fu, Lois E. H. Smith, Timothy Hla
Summary: This study reveals the significance of S1P in vascular development. Activation of endothelial S1PR1 by circulating HDL-S1P can suppress neovascularization in retinopathy. These findings suggest that circulating HDL-S1P activation of endothelial S1PR1 serves as a protective mechanism against neovascular retinopathy.
EMBO MOLECULAR MEDICINE
(2023)