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

Jinwook Choi, Young-Kook Kim, Kyungsoo Park, Jinwoo Nah, Sung-Soo Yoon, Dong-Wook Kim, V. Narry Kim and Rho Hyun Seong

Key Points

  • Expression of miR-139-5p is downregulated in BCR-ABL–mediated CML patients.

  • miR-139-5p regulates proliferation and differentiation activities by targeting Brg1 in early hematopoiesis.

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.

  • Submitted February 26, 2016.
  • Accepted September 2, 2016.
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