Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway.
The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells. High expression of Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was observed in the U937 cell line. We transduced K562 cells with two independent adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell cycle arrest by increasing the expression of p21 and decreasing the expression of cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore, Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK pathways, but no remarkable change in p-AKT was observed. These data provide evidence that Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment.
Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, 1#, Yixueyuan Road, Chongqing 400016, China.
Huijuan
H
Zhang
Shi
S
Tan
Juan
J
Wang
Shana
S
Chen
Jing
J
Quan
Jingrong
J
Xian
Shuai shuai
Ss
Zhang
Jingang
J
He
Ling
L
Zhang
D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D057809:HEK293 Cells; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D020298:U937 Cells
C438151:MSI2 protein, human; D016601:RNA-Binding Proteins; D020928:Mitogen-Activated Protein Kinases
AML; Apoptosis; CML; FITC; HSCs; K562; Leukemia; MAPK; MTT; Msi; Msi2; Musashi; Musashi2; Proliferation; acute myeloid leukemia; chronic myelogenous leukemia; fluorescein isothiocyanate; hematopoietic stem cells; methyl thiazolyl tetrazolium solution; mitogen-activated protein kinase