miR-17-92 promotes leukemogenesis in chronic myeloid leukemia via targeting A20 and activation of NF-κB signaling
- Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850 (China)
- Department of Oncology, PLA General Hospital, Beijing 100853 (China)
- Department of Hematology, General Hospital of Chinese Air Force, Beijing 100142 (China)
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 {sup +} 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. - Highlights: • Genomic depletion of miR-17-92 inhibits the BCR-ABL induced leukemogenesis in a mouse CML model. • miR-19b targets A20 to regulate NF-κB signaling in CML cells. • A20 functions as a suppressor in regulating CML cell growth and survival.
- OSTI ID:
- 22697057
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 487, Issue 4; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Anthelmintic drug niclosamide enhances the sensitivity of chronic myeloid leukemia cells to dasatinib through inhibiting Erk/Mnk1/eIF4E pathway
NF-κB mediated miR-130a modulation in lung microvascular cell remodeling: Implication in pulmonary hypertension