title: Leukemia Stem Cell-Released Microvesicles Promote the Survival and Migration of Myeloid Leukemia Cells and These Effects Can Be Inhibited by MicroRNA34a Overexpression.
abstract: Leukemia stem cells (LSCs) play the major role in relapse of acute myeloid leukemia (AML). Recent evidence indicates that microvesicles (MVs) released from cancer stem cells can promote tumor growth and invasion. In this study, we investigated whether LSCs-released MVs (LMVs) can regulate the malignance of AML cells and whether overexpression of tumor suppressive microRNA (miR), miR34a, is able to interrupt this process. LSCs were transfected with miRNA control (miRCtrl) or miR34a mimic for producing LMVs, respectively, defined as LMVs(miRCtrl) and LMVs(miR34a). The effect of miR34a transfection on LSC proliferation and the effects of LMVs(miRCtrl) or LMVs(miR34a) on the proliferation, migration, and apoptosis of AML cells (after LSC depletion) were determined. The levels of miR34a targets, caspase-3 and T cell immunoglobulin mucin-3 (Tim-3), were analyzed. Results showed that (1) LMVs(miRCtrl) promoted proliferation and migration and inhibited apoptosis of AML cells, which were associated with miR34a deficit; (2) transfection of miR34a mimic inhibited LSC proliferation and increased miR34a level in LMVs(miR34a); (3) LMVs(miR34a) produced opposite effects as compared with LMVs(miRCtrl), which were associated with the changes of caspase-3 and Tim-3 levels. In summary, LMVs support AML cell malignance and modulating miR34a could offer a new approach for the management of AML.
authors.affiliation: Department of Hematology, The Affiliated Hospital of Guilin Medical College, Guilin, Guangxi 541001, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Guilin Medical College, Guilin, Guangxi 541001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dong