miR-183-5p Inhibits Occurrence and Progression of Acute Myeloid Leukemia via Targeting Erbin
Authors: Weiying Gu
Jingting Jiang
Zhuojun Zheng
Xiaoyan Gu
Xiao Zheng
Yuandong Zhu
Xiaobao Xie
Wenwei Hu
Journal: Molecular Therapy (2019)
Discipline: CLINICAL MEDICINE
Keywords: AML; Erbin; differentiation; miR-183-5p; proliferation.
Affiliations: Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China; Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China; Cancer Immunotherapy Engineering Research Center of Jiangsu Province, Changzhou, Jiangsu Province, China; Institute of Cell Therapy, Soochow University, Changzhou, Jiangsu Province, China., Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China; Cancer Immunotherapy Engineering Research Center of Jiangsu Province, Changzhou, Jiangsu Province, China; Institute of Cell Therapy, Soochow University, Changzhou, Jiangsu Province, China., Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China., Department of Hematology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China. Electronic address: ., Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China; Cancer Immunotherapy Engineering Research Center of Jiangsu Province, Changzhou, Jiangsu Province, China; Institute of Cell Therapy, Soochow University, Changzhou, Jiangsu Province, China. Electronic address: .

Abstract:  Erbin has been shown to have significant effects on the development of solid tumors. However, little is known about its function and regulatory mechanism in hematological malignancies. The biological function of Erbin on cell proliferation was measured in vitro and in vivo. The predicted target of Erbin was validated by dual-luciferase reporter assay and rescue experiment. We found that overexpression of Erbin could inhibit the cell proliferation and promote the cell differentiation of acute myeloid leukemia (AML) cells, whereas depletion of Erbin could enhance the cell proliferation and block the cell differentiation in AML cells in vitro and in vivo. Besides, miR-183-5p was identified as the upstream regulator that negatively regulated the Erbin expression. The results were confirmed by dual-luciferase reporter and RNA pull-down assay. Furthermore, we found that miR-183-5p negatively regulated Erbin, resulting in enhanced cell proliferation of AML cells via activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways. The activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways was mediated by Erbin interacting with Grb2. These results were also validated by rescue experiments in vitro and in vivo. All above-mentioned findings indicated that the miR-183-5p/Erbin signaling pathway might represent a novel prognostic biomarker or therapeutic target for treatment of AML. 

Retracted: No

PubPeer comments:
 The tumors presented in Figure 8c are reused from another article from the same group (Zheng X et al., 2019; Mol Cancer; Figure 7a). The tumors have been manipulated and presented as something else. ![file] ,