MicroRNA-139-5p regulates proliferation of hematopoietic progenitors and is repressed during BCR-ABL-mediated leukemogenesis.
MicroRNAs (miRNAs) have emerged as important regulators of the immune system. However, despite this prominence, our understanding of the function of miRNAs in the early hematopoietic stages is incomplete. In this study, we found that miR-139-5p negatively regulated the proliferation of hematopoietic stem cells and progenitor cells and that downregulation of miR-139-5p expression was associated with hematopoietic malignancy, such as chronic myeloid leukemia (CML). Knockdown of miR-139-5p resulted in myeloid-biased differentiation with expansion of myeloid progenitor cells. In contrast, miR-139-5p expression inhibited the proliferation of hematopoietic progenitors and resulted in the remission of a CML-like disease that is induced by breakpoint cluster region-Abelson (BCR-ABL) transformation. We also found that Brg1 is a functional target of miR-139-5p and that Brg1 is involved in BCR-ABL-induced leukemogenesis. Thus, our results identify miR-139-5p as a key regulator of cellular proliferation during early hematopoiesis and suggest that it is a potent antileukemic molecule.
School of Biological Sciences, Institute for Molecular Biology and Genetics.
Jinwook
J
Choi
School of Biological Sciences, Institute for Molecular Biology and Genetics, Center for RNA Research, Institute for Basic Science, and.
Young-Kook
YK
Kim
School of Biological Sciences, Institute for Molecular Biology and Genetics.
Kyungsoo
K
Park
School of Biological Sciences, Institute for Molecular Biology and Genetics.
Jinwoo
J
Nah
Department of Internal Medicine, College of Medicine, Seoul National University, Seoul, Korea; and.
Sung-Soo
SS
Yoon
Department of Hematology, Seoul St. Mary's Hospital, Leukemia Research Institute, The Catholic University of Korea, Seoul, Korea.
Dong-Wook
DW
Kim
School of Biological Sciences, Institute for Molecular Biology and Genetics, Center for RNA Research, Institute for Basic Science, and.
V Narry
VN
Kim
School of Biological Sciences, Institute for Molecular Biology and Genetics.
Rho Hyun
RH
Seong
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D002469:Cell Separation; D015536:Down-Regulation; D005434:Flow Cytometry; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D055785:Gene Knockdown Techniques; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D015151:Immunoblotting; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
C555098:MIRN139 microRNA, human; C546202:MIRN139 microRNA, mouse; D035683:MicroRNAs; D016044:Fusion Proteins, bcr-abl