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The ZNF304-integrin axis protects against anoikis in cancer

NATURE COMMUNICATIONS 2015年第1期6卷 7351-7351页

作者： Aslan, Burcu Monroig, Paloma Hsu, Ming-Chuan Pena, Guillermo Armaiz Rodriguez-Aguayo, Cristian Gonzalez-Villasana, Vianey Rupaimoole, Rajesha Nagaraja, Archana Sidalaghatta Mangala, Selanere Han, Hee-Dong Yuca, Erkan Wu, Sherry Y. Ivan, Cristina Moss, Tyler J. Ram, Prahlad T. Wang, Huamin Gol-Chambers, Alexandra Ozkayar, Ozgur Kanlikilicer, Pinar Fuentes-Mattei, Enrique Kahraman, Nermin Pradeep, Sunila Ozpolat, Bulent Tucker, Susan Hung, Mien-Chie Baggerly, Keith Bartholomeusz, Geoffrey Calin, George Sood, Anil K. Lopez-Berestein, Gabriel Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Grad Sch Biomed Sci Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA Univ Puerto Rico Sch Med San Juan PR 00936 USA Univ Texas MD Anderson Canc Ctr Dept Mol & Cellular Oncol Houston TX 77030 USA Natl Hlth Res Inst Natl Inst Canc Res Tainan 704 Taiwan Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Canc Biol Houston TX 77030 USA Konkuk Univ Sch Med Dept Immunol Chungcheongbukdo 380701 South Korea Univ Texas MD Anderson Canc Ctr Dept Invest Canc Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Syst Biol Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Pathol Houston TX 77030 USA Hacettepe Univ Sch Med Dept Pathol TR-06100 Ankara Turkey Univ Texas MD Anderson Canc Ctr Dept Bioinformat & Computat Biol Houston TX 77030 USA China Med Univ Ctr Mol Med Taichung 404 Taiwan China Med Univ Inst Canc Biol Taichung 404 Taiwan

Ovarian cancer (OC) is a highly metastatic disease, but no effective strategies to target this process are currently available. Here, an integrative computational analysis of the Cancer Genome Atlas OC data set and experimental validation identifies a zinc finger transcription factor ZNF304 associated with OC metastasis. High tumoral ZNF304 expression is associated with poor overall survival in OC patients. Through reverse phase protein array analysis, we demonstrate that ZNF304 promotes multiple proto-oncogenic pathways important for cell survival, migration and invasion. ZNF304 transcriptionally regulates beta 1 integrin, which subsequently regulates Src/focal adhesion kinase and paxillin and prevents anoikis. In vivo delivery of ZNF304 sirna by a dual assembly nanoparticle leads to sustained gene silencing for 14 days, increased anoikis and reduced tumour growth in orthotopic mouse models of OC. Taken together, ZNF304 is a transcriptional regulator of beta 1 integrin, promotes cancer cell survival and protects against anoikis in OC.

关键词： Apoptosis Cell signalling Ovarian cancer Targeted therapies

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A total transcriptome profiling method for plasma-derived extracellular vesicles: applications for liquid biopsies

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SCIENTIFIC REPORTS 2017年第1期7卷 14395-14395页

作者： Amorim, Maria G. Valieris, Renan Drummond, Rodrigo D. Pizzi, Melissa P. Freitas, Vanessa M. Sinigaglia-Coimbra, Rita Calin, George A. Pasqualini, Renata Arap, Wadih Silva, Israel T. Dias-Neto, Emmanuel Nunes, Diana N. AC Camargo Canc Ctr Lab Med Genom Sao Paulo SP Brazil AC Camargo Canc Ctr Lab Computat Biol Sao Paulo SP Brazil Univ Sao Paulo Inst Biomed Sci Dept Cell & Dev Biol Sao Paulo SP Brazil Univ Fed Sao Paulo Electron Microscopy Ctr Sao Paulo SP Brazil Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNAs Houston TX 77030 USA Univ New Mexico Comprehens Canc Ctr Albuquerque NM 87131 USA Univ New Mexico Sch Med Div Hematol Oncol Dept Internal Med Albuquerque NM 87131 USA Univ New Mexico Sch Med Div Mol Med Dept Internal Med Albuquerque NM 87131 USA Rockefeller Univ Lab Mol Immunol 1230 York Ave New York NY 10021 USA FMUSP Lab Neurociencias Alzira Denise Hertzog Silva LIM Inst Psiquiatria Sao Paulo SP Brazil

Extracellular vesicles (EVs) are key mediators of intercellular communication. Part of their biological effects can be attributed to the transfer of cargos of diverse types of rnas, which are promising diagnostic and prognostic biomarkers. EVs found in human biofluids are a valuable source for the development of minimally invasive assays. However, the total transcriptional landscape of EVs is still largely unknown. Here we develop a new method for total transcriptome profiling of plasma-derived EVs by next generation sequencing (NGS) from limited quantities of patient-derived clinical samples, which enables the unbiased characterization of the complete rna cargo, including both small- and long-rnas, in a single library preparation step. This approach was applied to rna extracted from EVs isolated by ultracentrifugation from the plasma of five healthy volunteers. Among the most abundant rnas identified we found small rnas such as trnas, mirnas and miscellaneous rnas, which have largely unknown functions. We also identified protein-coding and long noncoding transcripts, as well as circular rna species that were also experimentally validated. This method enables, for the first time, the full spectrum of transcriptome data to be obtained from minute patient-derived samples, and will therefore potentially allow the identification of cell-to-cell communication mechanisms and biomarkers.

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Correction to: Engineered probiotics

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Microbial cell factories 2022年第1期21卷 93页

作者： Junheng Ma Yuhong Lyu Xin Liu Xu Jia Fangyun Cui Xiaoheng Wu Shanshan Deng Changwu Yue Key Laboratory of Microbial Drugs Innovation and Transformation Medical College Yan'an University Yan'an 716000 Shaanxi China. Non‑Coding RNA and Drug Discovery Key Laboratory of Sichuan Province Chengdu Medical College Chengdu 610500 Sichuan China. School of Public Health Chengdu Medical College Chengdu 610500 Sichuan China. School of Basic Medical Sciences Chengdu Medical College Chengdu 610500 Sichuan China. Ecological Environmental Monitoring Center Luoyang 471000 Henan China. Non‑Coding RNA and Drug Discovery Key Laboratory of Sichuan Province Chengdu Medical College Chengdu 610500 Sichuan China. dssjx@***. Key Laboratory of Microbial Drugs Innovation and Transformation Medical College Yan'an University Yan'an 716000 Shaanxi China. changwuyue@***.

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miR-34a blocks osteoporosis and bone metastasis by inhibiting osteoclastogenesis and Tgif2

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Nature 2014年第7515期512卷 431-5页

作者： Jing Y Krzeszinski Wei Wei HoangDinh Huynh Zixue Jin Xunde Wang Tsung-Cheng Chang Xian-Jin Xie Lin He Lingegowda S Mangala Gabriel Lopez-Berestein Anil K Sood Joshua T Mendell Yihong Wan Department of Pharmacology The University of Texas Southwestern Medical Center Dallas Texas 75390 USA. Department of Molecular Biology The University of Texas Southwestern Medical Center Dallas Texas 75390 USA. Department of Clinical Sciences The University of Texas Southwestern Medical Center Dallas Texas 75390 USA. Division of Cellular and Developmental Biology Molecular and Cell Biology Department University of California at Berkeley Berkeley California 94705 USA. Center for RNA Interference and Non-coding RNA The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA. Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA. Department of Cancer Biology The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA. Simmons Cancer Center The University of Texas Southwestern Medical Center Dallas Texas 75390 USA. Simmons Cancer Center The University of Texas Southwestern Medical Center Dallas Texas 75390 USA.

Bone-resorbing osteoclasts significantly contribute to osteoporosis and bone metastases of cancer. Micrornas play important roles in physiology and disease, and present tremendous therapeutic potential. nonetheless, how micrornas regulate skeletal biology is underexplored. Here we identify miR-34a as a novel and critical suppressor of osteoclastogenesis, bone resorption and the bone metastatic niche. miR-34a is downregulated during osteoclast differentiation. Osteoclastic miR-34a-overexpressing transgenic mice exhibit lower bone resorption and higher bone mass. Conversely, miR-34a knockout and heterozygous mice exhibit elevated bone resorption and reduced bone mass. Consequently, ovariectomy-induced osteoporosis, as well as bone metastasis of breast and skin cancers, are diminished in osteoclastic miR-34a transgenic mice, and can be effectively attenuated by miR-34a nanoparticle treatment. Mechanistically, we identify transforming growth factor-β-induced factor 2 (Tgif2) as an essential direct miR-34a target that is pro-osteoclastogenic. Tgif2 deletion reduces bone resorption and abolishes miR-34a regulation. Together, using mouse genetic, pharmacological and disease models, we reveal miR-34a as a key osteoclast suppressor and a potential therapeutic strategy to confer skeletal protection and ameliorate bone metastasis of cancers.

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Chemical transformation motifs - Modelling pathways as integer hyperflows

arXiv

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arXiv 2017年

作者： Andersen, Jakob L. Flamm, Christoph Merkle, Daniel Stadler, Peter F. Earth-Life Science Institute Tokyo Institute of Technology Tokyo 152-8550 Japan Department of Mathematics and Computer Science University of Southern Denmark Odense M DK-5230 Denmark Research group Bioinformatics and Computational Biology Faculty of Computer Science University of Vienna Vienna 1090 Austria Institute for Theoretical Chemistry University of Vienna Wien 1090 Austria Halle-Jena-Leipzig and Competence Center for Scalable Data Services Solutions Dresden-Leipzig Leipzig Research Center for Civilization Diseases University of Leipzig Leipzig D-04107 Germany Max Planck Institute for Mathematics in the Sciences Leipzig D-04103 Germany Fraunhofer Institute for Cell Therapy and Immunology Leipzig D-04103 Germany Center for non-coding RNA in Technology and Health University of Copenhagen Frederiksberg C DK-1870 Denmark Santa Fe Institute 1399 Hyde Park Rd Santa Fe NM 87501 United States Research Network Chemistry Meets Microbiology University of Vienna Wien A-1090 Austria

We present an elaborate framework for formally modelling pathways in chemical reaction networks on a mechanistic level. Networks are modelled mathematically as directed multi-hypergraphs, with vertices corresponding to molecules and hyperedges to reactions. Pathways are modelled as integer hyperflows and we expand the network model by detailed routing constraints. In contrast to the more traditional approaches like Flux Balance Analysis or Elementary Mode analysis we insist on integer-valued flows. While this choice makes it necessary to solve possibly hard integer linear programs, it has the advantage that more detailed mechanistic questions can be formulated. It is thus possible to query networks for general transformation motifs, and to automatically enumerate optimal and near-optimal pathways. Similarities and differences between our work and traditional approaches in metabolic network analysis are discussed in detail. To demonstrate the applicability of the mathematical framework to real-life problems we first explore the design space of possible non-oxidative glycolysis pathways and show that recent manually designed pathways can be further optimised. We then use a model of sugar chemistry to investigate pathways in the autocatalytic formose process. A graph transformation-based approach is used to automatically generate the reaction networks of interest. Copyright © 2017, The Authors. All rights reserved.

关键词： Integer programming

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DNA origami technology for biomedical applications: Challenges and opportunities

MedComm - Biomaterials and Applications

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MedComm - Biomaterials and Applications 2023年第2期2卷

作者： Li, Ling Nie, Shihong Du, Ting Zhao, Jiaxuan Chen, Xiaoyuan West China School of Public Health West China Fourth Hospital and State Key Laboratory of Biotherapy Sichuan University Chengdu China Department of Radiation Oncology Cancer Center West China Hospital Sichuan University Chengdu China Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province Chengdu Medical College Chengdu China Departments of Diagnostic Radiology Surgery Chemical and Biomolecular Engineering and Biomedical Engineering Yong Loo Lin School of Medicine and Faculty of Engineering National University of Singapore Singapore Singapore Clinical Imaging Research Centre Centre for Translational Medicine Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore Nanomedicine Translational Research Program NUS Center for Nanomedicine Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore Institute of Molecular and Cell Biology Agency for Science Technology and Research (A*STAR) Singapore Singapore

DNA origami, a promising branch of structural DNA technology, refers to the technique of folding a single-stranded DNA scaffold into well-defined nanostructures. In recent years, DNA origami nanostructures have shown considerable promise in a variety of biomedical applications, owing to their biodegradability, unique programmability, and addressability. Despite their popularity, the biomedical application of DNA origami techniques, which exploits their unique programmability and addressability, is rare in previous studies. Most recently, mounting evidence has demonstrated the robustness of DNA origami nanostructures in the spatial organization of functional components at the nanoscale in the biomedical field. These examples provide typical paradigms to fully realize the potential of DNA origami techniques by taking advantage of their unique programmability and addressability. This minireview summarizes the recent advancements of DNA origami techniques in biosensing, biocatalysis, and drug delivery, and the representative examples using DNA origami nanostructures for the spatial organization of functional molecules with nanometric precision are highlighted. We further discuss the possible limitations and challenges for in vivo applications, including stability issues and potential immunogenicity, and finally, propose some strategies to overcome these obstacles to fully realize the potential of DNA origami techniques in biomedical applications. © 2023 The Authors. MedComm – Biomaterials and Applications published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).

关键词： biocatalysis biosensing DNA nanotechnology DNA origami

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Overcoming adaptive resistance to anti-VEGF therapy by targeting CD5L

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NATURE COMMUNICATIONS 2023年第1期14卷 2407页

作者： LaFargue, Christopher J. Amero, Paola Noh, Kyunghee Mangala, Lingegowda S. Wen, Yunfei Bayraktar, Emine Umamaheswaran, Sujanitha Stur, Elaine Dasari, Santosh K. Ivan, Cristina Pradeep, Sunila Yoo, Wonbeak Lu, Chunhua Jennings, Nicholas B. Vathipadiekal, Vinod Hu, Wei Chelariu-Raicu, Anca Ku, Zhiqiang Deng, Hui Xiong, Wei Choi, Hyun-Jin Hu, Min Kiyama, Takae Mao, Chai-An Ali-Fehmi, Rouba Birrer, Michael J. Liu, Jinsong Zhang, Ningyan Lopez-Berestein, Gabriel de Franciscis, Vittorio An, Zhiqiang Sood, Anil K. Univ Texas MD Anderson Canc Ctr Dept Gynecol Oncol & Reprod Med Houston TX 77030 USA Univ Texas MD Anderson Canc Ctr Dept Expt Therapeut Houston TX 77030 USA CNR Ist Endocrinol Oncol Sperimentale Naples Italy Korea Res Inst Biosci & Biotechnol Lab Dis Modeling & Therapeut Daejeon South Korea Univ Texas MD Anderson Canc Ctr Ctr RNA Interference & Non Coding RNA Houston TX 77030 USA Med Coll Wisconsin Dept Obstet & Gynecol Milwaukee WI 53226 USA Univ Texas MD Anderson Canc Ctr Dept Mol & Cellular Oncol Houston TX 77030 USA Wave Life Sci 733 Concord Ave Cambridge MA 02138 USA Alloy Therapeut Dept Genet Med Waltham MA USA Ludwig Maximilians Univ Munchen Dept Obstet & Gynecol Munich Germany German Canc Res Ctr German Canc Consortium DKTK Munich Germany Univ Texas Hlth Sci Ctr Houston Texas Therapeut Inst Brown Fdn Inst Mol Med Houston TX 77030 USA Chung Ang Univ Coll Med Dept Obstet & Gynecol Seoul South Korea Chung Ang Univ Coll Med Gwangmyeong Hosp Dept Obstet & Gynecol Seoul South Korea Univ Texas MD Anderson Canc Ctr CPRIT Single Core Dept Genet Houston TX 77030 USA Univ Texas Hlth Sci Ctr Houston UTHealth Ruiz Dept Ophthalmol & Visual Sci McGovern Med Sch Houston TX 77030 USA MD Anderson Canc Ctr UTHealth Grad Sch Biomed Sci Houston TX 77030 USA Wayne State Univ Dept Pathol Detroit MI 48201 USA Univ Arkansas Med Sci Winthrop P Rockefeller Canc Inst Little Rock AR USA Univ Texas MD Anderson Canc Ctr Dept Pathol Houston TX 77030 USA Natl Res Council CNR Inst Genet & Biomed Res IRGB UOS Milan Via R Levi Montalcini I-20090 Pieve Emanuele MI Italy Harvard Med Sch Initiat RNA Med Boston MA 02115 USA

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression;however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an rna-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility. The efficacy of antiangiogenic therapy in the clinic is often limited by the emergence of resistance. Here, the authors show that in ovarian cancer anti-VEGF inhibitors induce the overexpression of CD5L in endothelial cells through hypoxia-driven PPARy activation and that blocking CD5L can overcome resistance.

关键词： Cancer Cancer microenvironment

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Author Correction: Hypoxia-mediated downregulation of mirna biogenesis promotes tumour progression

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Nature communications 2020年第1期11卷 2867页

作者： Rajesha Rupaimoole Sherry Y Wu Sunila Pradeep Cristina Ivan Chad V Pecot Kshipra M Gharpure Archana S Nagaraja Guillermo N Armaiz-Pena Michael McGuire Behrouz Zand Heather J Dalton Justyna Filant Justin Bottsford Miller Chunhua Lu Nouara C Sadaoui Lingegowda S Mangala Morgan Taylor Twan van den Beucken Elizabeth Koch Cristian Rodriguez-Aguayo Li Huang Menashe Bar-Eli Bradly G Wouters Milan Radovich Mircea Ivan George A Calin Wei Zhang Gabriel Lopez-Berestein Anil K Sood Department of Gynecologic Oncology The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. Graduate School of Biomedical Sciences The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. Department of Molecular Therapeutics University of North Carolina Lineberger Comprehensive Cancer Center 101 Manning Drive Chapel Hill NC 27599 USA. Department of Medical Biophysics University of Toronto Toronto ON Canada M5G 1L7. Princess Margaret Cancer Centre and Campbell Family Institute for Cancer Research University Health Network Toronto ON Canada M5G 1L7. Department of Experimental Therapeutics The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. Department of Cancer Biology The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. Department of Surgery Microbiology and Immunology Indiana University 980W Walnut Street Indianapolis IN 46202 USA. Department of Medicine Microbiology and Immunology Indiana University 980W Walnut Street Indianapolis IN 46202 USA. Department of Pathology The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. Department of Gynecologic Oncology The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. asood@***. Center for RNA Interference and Non-Coding RNA The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. asood@***. Department of Cancer Biology The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard Houston TX 77030 USA. asood@***.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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

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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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