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Hypoxia promotes stem cell phenotypes and poor prognosis through epigenetic regulation of DICER

NATURE COMMUNICATIONS 2014年第Oct.期5卷 5203-5215页

作者： van den Beucken, Twan Koch, Elizabeth Chu, Kenneth Rupaimoole, Rajesha Prickaerts, Peggy Adriaens, Michiel Voncken, Jan Willem Harris, Adrian L. Buffa, Francesca M. Haider, Syed Starmans, Maud H. W. Yao, Cindy Q. Ivan, Mircea Ivan, Cristina Pecot, Chad V. Boutros, Paul C. Sood, Anil K. Koritzinsky, Marianne Wouters, Bradly G. Princess Margaret Canc Ctr Toronto ON M5G IL7 Canada Campbell Family Inst Canc Res Univ Hlth Network Toronto ON M5G IL7 Canada Maastricht Univ Med Ctr GROW Sch Oncol & Dev Biol Dept Radiat Oncol NL-6200 MD Maastricht Netherlands Maastricht Univ Med Ctr GROW Sch Oncol & Dev Biol Dept Toxicogen NL-6200 MD Maastricht Netherlands Univ Toronto Dept Med Biophys Toronto ON M5G 1L7 Canada Ontario Inst Canc Res Informat & Biocomp Program Toronto ON M5G 1L7 Canada Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA Univ Amsterdam Acad Med Ctr Heart Failure Res Ctr Dept Expt Cardiol NL-1105 AZ Amsterdam Netherlands Maastricht Univ BiGCaT Dept Bioinformat NL-6200 MD Maastricht Netherlands Maastricht Univ BiGCaT Dept Bioinformat NL-6200 MD Maastricht Netherlands John Radcliffe Hosp Weatherall Inst Mol Med Canc Res UK Dept Oncol Oxford OX3 9DS England Indiana Univ Melvin & Bren Simon Canc Ctr Dept Med Indianapolis IN 46202 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Thorac Head & Neck Oncol Houston TX 77030 USA Univ Toronto Dept Pharmacol & Toxicol Toronto ON M5S 1A8 Canada Univ Toronto Inst Med Sci Toronto ON M5S 1A8 Canada Univ Toronto Dept Radiat Oncol Toronto ON M5T 1P5 Canada Ontario Inst Canc Res Select Therapies Program Toronto ON M5G 1L7 Canada

Micrornas are small regulatory rnas that post transcriptionally control gene expression. Reduced expression of DICER, the enzyme involved in microrna processing, is frequently observed in cancer and is associated with poor clinical outcome in various malignancies. Yet, the underlying mechanisms are not well understood. Here we identify tumour hypoxia as a regulator of DICER expression in large cohorts of breast cancer patients. We show that DICER expression is suppressed by hypoxia through an epigenetic mechanism that involves inhibition of oxygen-dependent H3K27me3 demethylases KDM6A/B and results in silencing of the DICER promoter. Subsequently, reduced mirna processing leads to derepression of the miR-200 target ZEB1, stimulates the epithelial to mesenchymal transition and ultimately results in the acquisition of stem cell phenotypes in human mammary epithelial cells. Our study uncovers a previously unknown relationship between oxygen-sensitive epigenetic regulators, mirna biogenesis and tumour stem cell phenotypes that may underlie poor outcome in breast cancer.

关键词： EPITHELIAL-MESENCHYMAL TRANSITION DEMETHYLASE JMJD3 CONTRIBUTES BREAST-CANCER EXPRESSION PROFILES SOMATIC MUTATIONS INDUCIBLE FACTORS DOWN-REGULATION OVARIAN-CANCER METASTASIS EZH2 Stem Cells Ovary Cancer Somatic Mutation Epithelial-Mesenchymal Transition Derepression Hypoxia Epigenetic Processes Regulators poor prognosis Phenotype Breast Cancer Down-Regulation metastasis Micrornas Epigenetics

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Corrigendum to “ApoptomiRs expression modulated by BCR–ABL is linked to CML progression and imatinib resistance” [Blood Cells Mol. Dis. 53 (1–2) (June–August 2014) 47–55]

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Blood Cells, Molecules, and Diseases 2015年第4期55卷 420-420页

作者： A.F. Ferreira L.G. Moura I. Tojal L. Ambrósio B. Pinto-Simões N. Hamerschlak G.A. Calin C. Ivan D.T. Covas S. Kashima F.A. Castro Departamento de Análises Clínicas Toxicológicas e Bromatológicas Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo Brazil Centro Regional de Hemoterapia de Ribeirão Preto Brazil Departamento de Clínica Médica Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo Brazil Hospital Israelita Albert Einstein São Paulo Brazil Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston TX USA Center for RNA Interference and Non-Coding RNAs The University of Texas MD Anderson Cancer Center Houston TX USA

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Regulation of cellular sterol homeostasis by the oxygen responsive noncoding rna lincNORS (vol 1, 4755, 2020)

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NATURE COMMUNICATIONS 2020年第1期11卷 4755-4755页

作者： Wu, Xue Niculite, Cristina M. Preda, Mihai Bogdan Rossi, Annalisa Tebaldi, Toma Butoi, Elena White, Mattie K. Tudoran, Oana M. Petrusca, Daniela N. Jannasch, Amber S. Bone, William P. Zong, Xingyue Fang, Fang Burlacu, Alexandrina Paulsen, Michelle T. Hancock, Brad A. Sandusky, George E. Mitra, Sumegha Fishel, Melissa L. Buechlein, Aaron Ivan, Cristina Oikonomopoulos, Spyros Gorospe, Myriam Mosley, Amber Radovich, Milan Dave, Utpal P. Ragoussis, Jiannis Nephew, Kenneth P. Mari, Bernard McIntyre, Alan Konig, Heiko Ljungman, Mats Cousminer, Diana L. Macchi, Paolo Ivan, Mircea Department of Microbiology and Immunology Indiana University School of Medicine Indianapolis IN 46202 USA Department of Medicine Indiana University School of Medicine Indianapolis IN 46202 USA “Victor Babes” National Institute of Pathology Bucharest Romania Institute of Cellular Biology and Pathology “Nicolae Simionescu” Bucharest Romania Laboratory of Molecular and Cellular Neurobiology Department of Cellular Computational and Integrative Biology - CIBIO University of Trento Trento Italy Laboratory of Translational Genomics Department of Cellular Computational and Integrative Biology - CIBIO University of Trento Trento Italy Yale Cancer Center Yale University School of Medicine New Haven CT 06520 USA The Oncology Institute “Prof Dr. Ion Chiricuta” Cluj-Napoca Romania Metabolite Profiling Facility Bindley Bioscience Center Purdue University West Lafayette IN 47907 USA Department of Genetics Department of Systems Pharmacology and Translational Therapeutics Institute of Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Department of Cellular and Integrative Physiology Indiana University School of Medicine Indianapolis IN USA Departments of Radiation Oncology and Environmental Health Sciences Center for RNA Biomedicine University of Michigan Ann Arbor MI 48109 USA Department of Surgery Indiana University School of Medicine Indianapolis IN 46202 USA Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis IN 46202 USA Melvin and Bren Simon Cancer Center Indiana University Indianapolis IN USA Department of Obstetrics and Gynecology Indiana University School of Medicine Indianapolis IN 46202 USA Department of Pharmacology and Toxicology Department of Pediatrics Wells Center for Pediatric Research Indiana University School of Medicine Indianapolis IN 46202 USA Indiana University Center for Genomics and Bioinformatics Bloomington IN 47405 USA Center

We hereby provide the initial portrait of lincNORS, a spliced lincrna generated by the MIR193BHG locus, entirely distinct from the previously described miR-193b-365a tandem. While inducible by low O2 in a variety of cells and associated with hypoxia in vivo, our studies show that lincNORS is subject to multiple regulatory inputs, including estrogen signals. Biochemically, this lincrna fine-tunes cellular sterol/steroid biosynthesis by repressing the expression of multiple pathway components. Mechanistically, the function of lincNORS requires the presence of RALY, an rna-binding protein recently found to be implicated in cholesterol homeostasis. We also noticed the proximity between this locus and naturally occurring genetic variations highly significant for sterol/steroid-related phenotypes, in particular the age of sexual maturation. An integrative analysis of these variants provided a more formal link between these phenotypes and lincNORS, further strengthening the case for its biological relevance. noncoding transcripts contribute to the adaptation of cellular processes to oxygen levels. Here the authors characterize a hypoxia responsive lncrna lincNORS and show that it has a role in cellular sterol homeostasis.

关键词： Long non-coding rnas Long non-coding rnas Homeostasis Homeostasis

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IT-22TARGETING THE IMMUNE CHECKPOINT NETWORK WITH miR-138 EXERTS THERAPEUTIC EFFICACY IN MURINE MODELS OF GLIOMA

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Neuro-Oncology 2014年第SUPPL_5期16卷 v114-v114页

作者： Nduom, Edjah K. Wei, Jun Kong, Ling-Yuan Xu, Shuo Gabrusiewicz, Konrad Ling, Xiaoyang Huang, Neal Qiao, Wei Zhou, Shouhao Ivan, Cristina Chen, Jie Qing Ji, Yongjie Radvanyi, Laszlo Fuller, Greg N. Gilbert, Mark Conrad, Charles A. Overwijk, Willem Calin, George A. Heimberger, Amy B. Department of Neurosurgery The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Neurosurgery Qilu Hospital of Shandong University Jinan China Department of Biostatistics The University of Texas M.D. Anderson Cancer Center Houston TX USA Center for RNA Interference and Non-Coding RNAs The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Melanoma Medical Oncology The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Neuro-Oncology The University of Texas M.D. Anderson Cancer Center Houston TX USA Department of Neuropathology The University of Texas M.D. Anderson Cancer Center Houston TX USA Depatment of Experimental Therapeutics The University of Texas M.D. Anderson Cancer Center Houston TX USA

Antibody therapeutic targeting of the immune checkpoints CTLA-4 and PD-1 has demonstrated marked tumor regression in clinical trials; however, this requires multimodality treatment and has known toxicity. Micrornas (mirnas) can modulate gene transcripts, including those of tumor-mediated immune suppressive pathways. Mirnas can be delivered to the systemic immune compartment, which can initiate anti-tumor immune response, overcoming the issue of mirna delivery to the tumor. To identify potential mirna therapeutics, we exploited human glioblastoma mirna expression assays followed by a screening process of predicted binding sites in the 3' UTR of immune suppressive pathways and immune checkpoints. MiR-138 emerged as a leading candidate with binding sites in the 3' UTR of CTLA-4 and PD-1, which were functionally confirmed with luciferase expression assays. The miR-138 targeting of CTLA-4 and PD-1 was further validated by expression analysis of transfected human CD4+ T cells. Using human glioma tumor microarrays and in situ hybridization, heterogeneous expression of miR-138 was found amongst all glioma grades and pathological subtypes. The PD-1 ligand, PD-L1, was frequently expressed in glioblastomas based on immunohistochemistry and ex vivo flow cytometry from human glioblastoma. Analysis of TCGA database revealed that co-expression of PD-1 and PD-L1 impacts glioblastoma survival. The role of CTLA-4 in glioblastoma-mediated immune suppression is well documented, suggesting that targeting of CTLA-4 and PD-1 with miR-138 in glioblastoma patients may have anti-tumor activity. In vivo treatment with miR-138 in immune-competent mice with GL261 gliomas demonstrated marked tumor regression, a 43% increase in median survival (P = 0.011), and an associated decrease in intratumoral FoxP3+ Tregs, CTLA-4, and PD-1 expression. Conversely, in an immune-incompetent animal background, miR-138 failed to exert any therapeutic effect, indicating that miR-138 mediates in vivo activity via

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Corrigendum to “Exenatide ameliorates hydrogen peroxide-induced pancreatic β-cell apoptosis through regulation of METTL3-mediated m 6 A methylation” [Eur. J. Pharmacol. 924 (2022) 174960]

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European Journal of Pharmacology 2023年 946卷

作者： Simin Zhou Yue Sun Yujie Xing Zhi Wang Shujun Wan Xinming Yao Qiang Hua Xiangjian Meng Jinhan Cheng Min Zhong Kun Lv Xiang Kong Department of Endocrinology The First Affiliated Hospital of Wannan Medical College Yijishan Hospital Wuhu 241001 China Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution Wannan Medical College Wuhu 241002 China Department of Cardiology The First Affiliated Hospital of Wannan Medical College Yijishan Hospital Wuhu 241001 China Central Laboratory of Yijishan Hospital Wuhu 241001 China Clinical Research Center for Critical Respiratory Medicine of Anhui Province Wannan Medical College Wuhu 241002 China

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Proceedings of the EuBIC-MS 2020 Developers’ Meeting

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EuPA Open Proteomics 2020年 24卷 1-6页

作者： Christopher Ashwood Wout Bittremieux Eric W. Deutsch Nadezhda T. Doncheva Viktoria Dorfer Ralf Gabriels Vladimir Gorshkov Surya Gupta Andrew R. Jones Lukas Käll Dominik Kopczynski Lydie Lane Ludwig Lautenbacher Marc Legeay Marie Locard-Paulet Bart Mesuere Yasset Perez-Riverol Eugen Netz Sander Willems European Bioinformatics Community for Mass Spectrometry (info@***) Denmark Department of Cellular and Integrative Physiology University of Nebraska Medical Center Omaha USA Department of Computer Science University of Antwerp Antwerp Belgium Institute for Systems Biology Seattle WA 98109 USA Novo Nordisk Foundation Center for Protein Research University of Copenhagen Denmark Bioinformatics Research Group University of Applied Sciences Upper Austria Hagenberg Austria VIB-UGent Center for Medical Biotechnology VIB Ghent Belgium Department of Biochemistry and Molecular Biology University of Southern Denmark Denmark Institute of Systems Molecular and Integrative Biology University of Liverpool UK Science for Life Laboratory KTH - Royal Institute of Technology Solna Stockholm Sweden Leibniz-Institut für Analytische Wissenschaften - ISAS - e.V. Dortmund Germany SIB-Swiss Institute of Bioinformatics and Department of Microbiology and Molecular Medicine Faculty of Medicine Geneva University Geneva Switzerland Technical University of Munich Chair for Proteomics and Bioanalytics Freising Germany European Molecular Biology Laboratory European Bioinformatics Institute (EMBL-EBI) Wellcome Trust Genome Campus Hinxton Cambridge CB10 1SD UK Applied Bioinformatics Dept. of Computer Science University of Tübingen Tübingen Germany Skaggs School of Pharmacy and Pharmaceutical Sciences University of California San Diego La Jolla CA 92093 USA Center for non-coding RNA in Technology and Health Department of Veterinary and Animal Sciences University of Copenhagen Denmark Department of Biomolecular Medicine Ghent University Ghent Belgium Department of Applied Mathematics Computer Science and Statistics Ghent University Ghent Belgium Biomolecular Interactions Max Planck Institute for Developmental Biology Tübingen Germany

The 2020 European Bioinformatics Community for Mass Spectrometry (EuBIC-MS) Developers’ meeting was held from January 13 th to January 17 th 2020 in Nyborg, Denmark. Among the participants were scientists as well as developers working in the field of computational mass spectrometry (MS) and proteomics. The 4-day program was split between introductory keynote lectures and parallel hackathon sessions. During the latter, the participants developed bioinformatics tools and resources addressing outstanding needs in the community. The hackathons allowed less experienced participants to learn from more advanced computational MS experts, and to actively contribute to highly relevant research projects. We successfully produced several new tools that will be useful to the proteomics community by improving data analysis as well as facilitating future research. All keynote recordings are available on https://***/10.5281/zenodo.3890181 .

关键词： Computational mass spectrometry Mass spectrometry Proteomics Bioinformatics Spectrum clustering Phosphoproteomics XIC extraction Proteomics graph networks Predicted spectra Metaproteomics Functional annotations Benchmark development

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Erratum to “Circulating Levels of Microrna from Children with Newly Diagnosed Type 1 Diabetes and Healthy Controls: Evidence That miR-25 Associates to Residual Beta-Cell Function and Glycaemic Control during Disease Progression”

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Journal of Diabetes Research 2012年第1期2012卷 672865-672865页

作者： Lotte B. Nielsen Cheng Wang Kaspar Sørensen Claus H. Bang-Berthelsen Lars Hansen Marie-Louise M. Andersen Philip Hougaard Anders Juul Chen-Yu Zhang Flemming Pociot Henrik B. Mortensen Department of Pediatrics Herlev Hospital 2730 Herlev Denmarkherlevhospital.dk Faculty of Health Sciences University of Copenhagen 2200 Copenhagen Denmarkku.dk Jiangsu Engineering Research Center for microRNA Biology and Biotechnology State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University Nanjing 210093 *** Department of Growth and Reproduction Rigshospitalet and Faculty of Health Sciences University of Copenhagen 2100 Copenhagen Denmarkku.dk Glostrup Research Institute Glostrup Hospital and Center for Non-Coding RNA in Technology and Health University of Copenhagen 2600 Glostrup Denmarkku.dk Department of Statistics University of Southern Denmark 5000 Odense Denmarksdu.dk

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Correction: Oblique lateral internal fusion combined with percutaneous pedicle screw fixation in severe lumbar spinal stenosis: clinical and radiographic outcome

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Journal of orthopaedic surgery and research 2023年第1期18卷 953页

作者： Chen Liu Yin Geng Yifeng Li Department of Spine Surgery First Affiliated Hospital of Wannan Medical College No. 2 Zheshan West Road Wuhu 241001 Anhui China. Spine Research Center of Wannan Medical College No. 22 Wenchang West Road Wuhu 241001 Anhui China. Key Laboratory of Non-Coding RNA Transformation Research of Anhui Higher Education Institution Wannan Medical College Wuhu 241001 Anhui China. Department of Spine Surgery First Affiliated Hospital of Wannan Medical College No. 2 Zheshan West Road Wuhu 241001 Anhui China. lyf_0209@***. Spine Research Center of Wannan Medical College No. 22 Wenchang West Road Wuhu 241001 Anhui China. lyf_0209@***.

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Correction: Oblique lateral internal fusion combined with percutaneous pedicle screw fixation in severe lumbar spinal stenosis: clinical and radiographic outcome

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Journal of orthopaedic surgery and research 2024年第1期19卷 790页

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Biomechanical research using advanced micro-nano devices: In-Vitro cell Characterization focus

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Journal of Advanced Research 2024年

作者： Yan, Shiqiang Lu, Yan An, Changming Hu, Wanglai Chen, Yaofeng Li, Ziwen Wei, Wenbo Chen, Zongzheng Zeng, Xianhai Xu, Wei Lv, Zhenghua Pan, Fan Gao, Wei Wu, Yongyan Shenzhen Institute of Otolaryngology & Key Laboratory of Otolaryngology Longgang Otolaryngology Hospital Guangdong Shenzhen 518172 China Center of Cancer Immunology Shenzhen Institute of Advanced Technology Chinese Academy of Sciences Guangdong Shenzhen 518055 China Department of Otolaryngology Head & Neck Surgery The First Hospital Jinzhou Medical University Liaoning Jinzhou 121001 China Shanxi Key Laboratory of Otorhinolaryngology Head and Neck Cancer Department of Otolaryngology Head & Neck Surgery First Hospital of Shanxi Medical University Shanxi Taiyuan 030001 China Department of Head and Neck Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100021 China Translational Research Institute People's Hospital of Zhengzhou University Academy of Medical Science Henan International Joint Laboratory of Non-coding RNA and Metabolism in Cancer Zhengzhou University Henan Zhengzhou 450003 China Shenzhen University General Hospital & Shenzhen University Clinical Medical Academy Shenzhen University Guangdong Shenzhen 518055 China College of Chemistry & Pharmacy Northwest A&F University Shaanxi Yangling 712100 China The First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital Guangdong Shenzhen 518035 China Department of Otolaryngology-Head and Neck Surgery Shandong Provincial ENT Hospital Shandong University Shandong Jinan 250022 China

Background: Cells in the body reside in a dynamic microenvironment subjected to various physical stimuli, where mechanical stimulation plays a crucial role in regulating cellular physiological behaviors and functions. Aim of Review: Investigating the mechanisms and interactions of mechanical transmission is essential for understanding the physiological and functional interplay between cells and physical stimuli. Therefore, establishing an in vitro biomechanical stimulation cell culture system holds significant importance for research related to cellular biomechanics. Key Scientific Concepts of Review: In this review, we primarily focused on various biomechanically relevant cell culture systems and highlighted the advancements and prospects in their preparation processes. Firstly, we discussed the types and characteristics of biomechanics present in the microenvironment within the human body. Subsequently, we introduced the research progress, working principles, preparation processes, potential advantages, applications, and challenges of various biomechanically relevant in vitro cell culture systems. Additionally, we summarized and categorized currently commercialized biomechanically relevant cell culture systems, offering a comprehensive reference for researchers in related fields. © 2024

关键词： Biomechanical stimulation Cell culture systems Cellular biomechanics In vitro models Microenvironment

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