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

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.

journal_name

Blood

journal_title

Blood

authors

Choi J,Kim YK,Park K,Nah J,Yoon SS,Kim DW,Kim VN,Seong RH

doi

10.1182/blood-2016-02-702464

subject

Has Abstract

pub_date

2016-10-27 00:00:00

pages

2117-2129

issue

17

eissn

0006-4971

issn

1528-0020

pii

blood-2016-02-702464

journal_volume

128

pub_type

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