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Biochem Biophys Res Commun. 2017 Jun 10;487(4):868-874. doi: 10.1016/j.bbrc.2017.04.144. Epub 2017 Apr 28.

miR-17-92 promotes leukemogenesis in chronic myeloid leukemia via targeting A20 and activation of NF-κB signaling.

Author information

1
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
2
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
3
Department of Oncology, PLA General Hospital, Beijing 100853, PR China.
4
Department of Hematology, General Hospital of Chinese Air Force, Beijing 100142, PR China.
5
Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; School of Nursing, Jilin University, Changchun, Jilin 130021, PR China; Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China. Electronic address: lishengwang@ymail.com.

Abstract

miR-17-92 cluster are overexpressed in hematological malignancies including chronic myeloid leukemia (CML). However, their roles and mechanisms that regulate BCR-ABL induced leukemogenesis remain unclear. In this study, we demonstrated that genomic depletion of miR-17-92 inhibited the BCR-ABL induced leukemogenesis by using a mouse model of transplantation of BCR-ABL transduced hematopoietic stem cells. Furthermore, we identified that miR-19b targeted A20 (TNFAIP3). A20 overexpression results in inactivation of NF-κB activity including decrease of phosphorylation of P65 and IκBα, leads to induce apoptosis and inhibit proliferation and cycle in CML CD34 + cells. Thus we proved that miR-17-92 is a critical contributor to CML leukemogenesis via targeting A20 and activation of NF-κB signaling. These findings indicate that miR-17-92 will be important resources for developing novel treatment strategies of CML and better understanding long-term disease control.

KEYWORDS:

A20; Chronic myeloid leukemia; NF-κB; miR-17-92

PMID:
28461114
DOI:
10.1016/j.bbrc.2017.04.144
[Indexed for MEDLINE]

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