例如:"lncRNA", "apoptosis", "WRKY"

Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells.

Cell Rep. 2020 Jun 23;31(12):107816
Zhigang Cai 1 , Fabiola Aguilera 2 , Baskar Ramdas 2 , Swapna Vidhur Daulatabad 3 , Rajneesh Srivastava 3 , Jonathan J Kotzin 4 , Martin Carroll 4 , Gerald Wertheim 4 , Adam Williams 5 , Sarath Chandra Janga 3 , Chi Zhang 6 , Jorge Henao-Mejia 7 , Reuben Kapur 8
Zhigang Cai 1 , Fabiola Aguilera 2 , Baskar Ramdas 2 , Swapna Vidhur Daulatabad 3 , Rajneesh Srivastava 3 , Jonathan J Kotzin 4 , Martin Carroll 4 , Gerald Wertheim 4 , Adam Williams 5 , Sarath Chandra Janga 3 , Chi Zhang 6 , Jorge Henao-Mejia 7 , Reuben Kapur 8
+ et al

[No authors listed]

Author information
  • 1 Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: zcai@iupui.edu.
  • 2 Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA.
  • 3 School of Informatics and Computing, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA.
  • 4 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • 5 The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
  • 6 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • 7 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Division of Protective Immunity, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • 8 Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: rkapur@iupui.edu.

摘要


Inhibition of anti-apoptotic proteins BCL-2 and MCL-1 to release pro-apoptotic protein BIM and reactivate cell death could potentially be an efficient strategy for the treatment of leukemia. Here, we show that a lncRNA, MORRBID, a selective transcriptional repressor of BIM, is overexpressed in human acute myeloid leukemia (AML), which is associated with poor overall survival. In both human and animal models, MORRBID hyperactivation correlates with two recurrent AML drivers, TET2 and FLT3ITD. Mice with individual mutations of Tet2 or Flt3ITD develop features of chronic myelomonocytic leukemia (CMML) and myeloproliferative neoplasm (MPN), respectively, and combined presence results in AML. We observe increased levels of Morrbid in murine models of CMML, MPN, and AML. Functionally, loss of Morrbid in these models induces increased expression of Bim and cell death in immature and mature myeloid cells, which results in reduced infiltration of leukemic cells in tissues and prolongs the survival of AML mice. Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

KEYWORDS: BIM, FLT3(ITD), MORRBID, TET2, apoptosis, leukemia, lncRNA