Open AccessTumor Suppressor DYRK1A Effects on Proliferation and Chemoresistance of AML Cells by Downregulating c-Myc
Author(s) -
Qiang Liu,
Na Liu,
Shaolei Zang,
Heng Liu,
Pin Wang,
Chunyan Ji,
Xiulian Sun
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0098853
Subject(s) - dyrk1a , myeloid leukemia , cancer research , cell growth , downregulation and upregulation , myeloid , haematopoiesis , bone marrow , cell culture , progenitor cell , leukemia , suppressor , biology , medicine , immunology , stem cell , kinase , microbiology and biotechnology , gene , cancer , genetics
Acute myeloid leukemia (AML), caused by abnormal proliferation and accumulation of hematopoietic progenitor cells, is one of the most common malignancies in adults. We reported here DYRK1A expression level was reduced in the bone marrow of adult AML patients, comparing to normal controls. Overexpression of DYRK1A inhibited the proliferation of AML cell lines by increasing the proportion of cells undergoing G0/G1 phase. We reasoned that the proliferative inhibition was due to downregulation of c-Myc by DYRK1A, through mediating its degradation. Moreover, overexpression of c-Myc markedly reversed AML cell growth inhibition induced by DYRK1A. DYRK1A also had significantly lower expression in relapsed/refractory AML patients, comparing to newly-diagnosed AML patients, which indicated the role of DYRK1A in chemoresistance of AML. Our study provided functional evidences for DYRK1A as a potential tumor suppressor in AML.