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

doi:10.1016/j.omtn.2020.04.013

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

Mol Ther Nucleic Acids. 2020 Jun 5:20:764-776. doi: 10.1016/j.omtn.2020.04.013. Epub 2020 May 1.

Authors

Yanan Wang¹, Jiamin Zhang¹, Yan Su¹, Chencong Wang¹, Gaochao Zhang¹, Xiao Liu¹, Qi Chen¹, Meng Lv¹, Yingjun Chang¹, Jun Peng², Ming Hou², Xiaojun Huang¹, Xiaohui Zhang³

Affiliations

¹ 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.
² Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China.
³ 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. Electronic address: zhangxh100@sina.com.

Abstract

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.