Research Paper Volume 11, Issue 10 pp 3376—3391
MicroRNA-335/ID4 dysregulation predicts clinical outcome and facilitates leukemogenesis by activating PI3K/Akt signaling pathway in acute myeloid leukemia
- 1 Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
- 2 Zhenjiang Clinical Research Center of Hematology, Zhenjiang, People’s Republic of China
- 3 The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Zhenjiang, People’s Republic of China
- 4 Department of Hematology, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
- 5 , Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, People’s Republic of China
- 6 Department of Geriatrics, The Second Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China
received: March 12, 2019 ; accepted: May 20, 2019 ; published: May 30, 2019 ;https://doi.org/10.18632/aging.101991
How to Cite
Copyright: Zhou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MircoRNA-335 (miR-335) has been reported as a significant cancer-associated microRNA, which was often epigenetically silenced and acted as a tumor suppressor gene in diverse human solid tumors. Conversely, recent studies show that miR-335 overexpression was identified in both adult and pediatric acute myeloid leukemia (AML), suggesting that it might play an oncogenic role of miR-335 in AML. However, the role of miR-335 during leukemogenesis remains to be elucidated. MiR-335/ID4 expression was detected by real-time quantitative PCR and/or western blot. Survival analysis was performed to explore the association between miR-335/ID4 expression and the prognosis, and further validated by public databases. Gain-of-function experiments determined by cell proliferation, apoptosis, and differentiation were conducted to investigate the biological functions of miR-335/ID4. Herein, we found that miR-335 expression, independent of its methylation, was significantly increased and negatively correlated with reduced ID4 expression in AML. Moreover, aberrant miR-335/ID4 expression independently affected chemotherapy response and leukemia-free/overall survival in patients with AML. Gain-of-function experiments in vitro showed the oncogenic role of miR-335 by affecting cell apoptosis and proliferation in AML, and could be rescued by ID4 restoration. Mechanistically, we identified and verified that miR-335/ID4 contributed to leukemogenesis through activating PI3K/Akt signaling pathway. Collectively, aberrant miR-335/ID4 expression was an independent prognostic biomarker in AML. MiR-335/ID4 dysregulation facilitated leukemogenesis through the activation of PI3K/Akt signaling pathway.