microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway
单位：[1]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China华中科技大学同济医学院附属协和医院[2]Department of Hematology and Oncology, National Cancer Center/National Clinical Research Cancer for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China北京大学深圳医院深圳市康宁医院深圳市南山区人民医院深圳医学信息中心中国医学科学院肿瘤医院深圳医院[3]Department of Hematology, The Affiliated Tianyou Hospital, Wuhan University of Science and Technology, Wuhan 430064, China[4]Department of Oncology Clinical Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA[5]Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China[6]Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center for Digestive Diseases, Beijing 100050, China临床科室国家中心肝病分中心首都医科大学附属北京友谊医院[7]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China华中科技大学同济医学院附属协和医院
Cancer cells-secreted extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in local and distant microenvironment. Our initial GEO database analysis identified the presence of differentially-expressed microRNA-1246 (miR-1246) in acute myeloid leukemia (AML) cell-derived EVs. Consequently, the current study set out to investigate the role of AML-derived EVs-packaged miR-1246 in leukemia stem cells (LSCs) bioactivities. The predicted binding between miR-1246 and LRIG1 was verified using dual luciferase reporter assay. Then, gain-and loss-of-function assays were performed in LSCs, where LSCs were co-cultured with AML cell-derived EVs to characterize the effects of miR-1246-containing EVs, miR-1246, LRIG1 and STAT3 pathway in LSCs. Our findings revealed, in AML cell-derived EVs, miR-1246 was highly-expressed and directly-targeted LRIG1 to activate the STAT3 pathway. MiR-1246 inhibitor or EV-encapsulated miR-1246 inhibitor was found to suppress the viability and colony formation abilities but promoted the apoptosis and differentiation of LSCs through inactivation of STAT3 pathway by up-regulating LRIG1. In addition, the inhibitory effects of AML cell-derived EVs carrying miR-1246 inhibitor on LSCs were substantiated by in vivo experiments. Collectively, our findings reveal that the repression of AML cell-derived EVs containing miR-1246 inhibitor alters the survival of LSCs by inactivating the LRIG1-mediated STAT3 pathway.
第一作者单位：[1]Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
通讯作者：
推荐引用方式(GB/T 7714)：
Chen Lijuan,Guo Zhi,Zhou Yongming,et al.microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway[J].AGING-US.2021,13(10):13644-13662.
APA：
Chen Lijuan,Guo Zhi,Zhou Yongming,Ni Jian,Zhu Jianhua...&Zhou Hao.(2021).microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway.AGING-US,13,(10)
MLA：
Chen Lijuan,et al."microRNA-1246-containing extracellular vesicles from acute myeloid leukemia cells promote the survival of leukemia stem cells via the LRIG1-meditated STAT3 pathway".AGING-US 13..10(2021):13644-13662
医学