miRNA-98-5p Targeting IGF2BP1 Induces Mesenchymal Stem Cell Apoptosis by Modulating PI3K/Akt and p53 in Immune Thrombocytopenia

Yanan Wang; Jiamin Zhang; Yan Su; Chencong Wang; Gaochao Zhang; Xiao Liu; Qi Chen; Meng Lv; Yingjun Chang; Jun Peng; Ming Hou; Xiaojun Huang; Xiaohui Zhang

Molecular Therapy: Nucleic Acids (Jun 2020)

miRNA-98-5p Targeting IGF2BP1 Induces Mesenchymal Stem Cell Apoptosis by Modulating PI3K/Akt and p53 in Immune Thrombocytopenia

Yanan Wang,
Jiamin Zhang,
Yan Su,
Chencong Wang,
Gaochao Zhang,
Xiao Liu,
Qi Chen,
Meng Lv,
Yingjun Chang,
Jun Peng,
Ming Hou,
Xiaojun Huang,
Xiaohui Zhang

Affiliations

Yanan Wang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Jiamin Zhang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Yan Su: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Chencong Wang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Gaochao Zhang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Xiao Liu: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Qi Chen: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Meng Lv: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Yingjun Chang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Jun Peng: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China
Ming Hou: Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China
Xiaojun Huang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China
Xiaohui Zhang: Peking University People’s Hospital, Peking University Institute of Hematology, Beijing 100044, China; National Clinical Research Center for Hematologic Disease, Beijing 100044, China; Collaborative Innovation Center of Hematology, Peking University, Beijing 100044, China; Corresponding author: Xiaohui Zhang, Peking University People’s Hospital, Peking University Institute of Hematology No. 11 Xizhimen South Street, Xicheng District, Beijing 100044, China.

Journal volume & issue: Vol. 20
pp. 764 – 776

Abstract

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Immune thrombocytopenia (ITP) is a common hematological autoimmune disease, in which defective mesenchymal stem cells (MSCs) are potentially involved. Our previous study suggested that MSCs in ITP patients displayed enhanced apoptosis. MicroRNAs (miRNAs) play important roles in ITP by affecting megakaryopoiesis, platelet production and immunoregulation, whereas the roles of miRNAs in ITP-MSCs remain unknown. In a previous study, we performed microarray analysis to obtain mRNA and miRNA profiles of ITP-MSCs. In the present study, we reanalyze the data and identify miR-98-5p as a candidate miRNA contributing to MSC deficiency in ITP. miR-98-5p acts through targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and the subsequent downregulation of insulin-like growth factor 2 (IGF-2) causes inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is involved in the process of MSC deficiency. Furthermore, miR-98-5p upregulates p53 by inhibiting β-transducin repeat-containing protein (β-TrCP)-dependent p53 ubiquitination. Moreover, miR-98-5p overexpression impairs the therapeutic effect of MSCs in ITP mice. All-trans retinoic acid (ATRA) protects MSCs from apoptosis by downregulating miR-98-5p, thus providing a potential therapeutic approach for ITP. Our findings demonstrate that miR-98-5p is a critical regulator of ITP-MSCs, which will help us thoroughly understand the pathogenesis of ITP.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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