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HOTTIP lncRNA Promotes Hematopoietic Stem Cell Self-Renewal Leading to AML-like Disease in Mice.
Luo, Huacheng; Zhu, Ganqian; Xu, Jianfeng; Lai, Qian; Yan, Bowen; Guo, Ying; Fung, Tsz Kan; Zeisig, Bernd B; Cui, Ya; Zha, Jie; Cogle, Christopher; Wang, Fei; Xu, Bing; Yang, Feng-Chun; Li, Wei; So, Chi Wai Eric; Qiu, Yi; Xu, Mingjiang; Huang, Suming.
Afiliación
  • Luo H; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
  • Zhu G; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136.
  • Xu J; Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
  • Lai Q; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
  • Yan B; Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA.
  • Guo Y; Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136; Department of Cell System & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
  • Fung TK; School of Cancer and Pharmaceutical Science, King's College London, London SE5 9NU, UK.
  • Zeisig BB; School of Cancer and Pharmaceutical Science, King's College London, London SE5 9NU, UK.
  • Cui Y; Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
  • Zha J; Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
  • Cogle C; Division of Hematology/Oncology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610, USA.
  • Wang F; Department of Hematology and Oncology, The Affiliated Zhongda Hospital, Southeast University Medical School, Nanjing 210009, China.
  • Xu B; Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China.
  • Yang FC; Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136; Department of Cell System & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Mays Cancer Center,
  • Li W; Department of Molecular and Cellular Biology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, USA.
  • So CWE; School of Cancer and Pharmaceutical Science, King's College London, London SE5 9NU, UK. Electronic address: eric.so@kcl.ac.uk.
  • Qiu Y; Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA. Electronic address: qiuy@ufl.edu.
  • Xu M; Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Department of Biochemistry and Molecular Biology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL 33136; Mays Cancer Center, Univers
  • Huang S; Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA; Penn State Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. Electronic address: shuang4@pennstatehealth.psu.edu.
Cancer Cell ; 36(6): 645-659.e8, 2019 12 09.
Article en En | MEDLINE | ID: mdl-31786140
Long non-coding RNAs (lncRNAs) are critical for regulating HOX genes, aberration of which is a dominant mechanism for leukemic transformation. How HOX gene-associated lncRNAs regulate hematopoietic stem cell (HSC) function and contribute to leukemogenesis remains elusive. We found that HOTTIP is aberrantly activated in acute myeloid leukemia (AML) to alter HOXA-driven topologically associated domain (TAD) and gene expression. HOTTIP loss attenuates leukemogenesis of transplanted mice, while reactivation of HOTTIP restores leukemic TADs, transcription, and leukemogenesis in the CTCF-boundary-attenuated AML cells. Hottip aberration in mice abnormally promotes HSC self-renewal leading to AML-like disease by altering the homeotic/hematopoietic gene-associated chromatin signature and transcription program. Hottip aberration acts as an oncogenic event to perturb HSC function by reprogramming leukemic-associated chromatin and gene transcription.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Regulación Leucémica de la Expresión Génica / ARN Largo no Codificante / Autorrenovación de las Células Límite: Animals Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mieloide Aguda / Regulación Leucémica de la Expresión Génica / ARN Largo no Codificante / Autorrenovación de las Células Límite: Animals Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos