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MicroRNA-139-5p regulates proliferation of hematopoietic progenitors and is repressed during BCR-ABL-mediated leukemogenesis

Cited 16 time in Web of Science Cited 17 time in Scopus
Authors
Choi, Jinwook; Kim, Young-Kook; Park, Kyungsoo; Nah, Jinwoo; Yoon, Sung-Soo; Kim, Dong-Wook; Kim, V. Narry; Seong, Rho Hyun
Issue Date
2016-10
Citation
Blood, Vol.128 No.17, pp.2117-2129
Abstract
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.
ISSN
0006-4971
URI
https://hdl.handle.net/10371/171868
DOI
https://doi.org/10.1182/blood-2016-02-702464
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Journal Papers (저널논문_생명과학부)
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