EMMPRIN is a widely distributed
cell surface glycoprotein, which plays an important role in
tumor progression and confers resistance to some chemotherapeutic drugs. Recent studies have shown that
EMMPRIN overexpression indicates poor prognosis in
acute myeloid leukemia (AML). However, little was known on the role of
EMMPRIN in
leukemia. Human
leukemia cell line U937 was stably transfected with a
EMMPRIN-targeted
shRNA-containing vector to investigate the effect of
EMMPRIN on cellular functions.
EMMPRIN expression was monitored by qRT-PCR and Western blotting. Cell viability and proliferation were determined by
trypan blue exclusion and
BrdU labeling, respectively. Cell cycle and apoptosis were analyzed by flow cytometry. Cytotoxicity of chemotherapeutic agent
adriamycin on cells was assessed by MTT assay. Knockdown of
EMMPRIN gene significantly inhibited cell viability and decreased cell proliferation. Fluorescence-activated cell-sorting analysis revealed that the reduced
EMMPRIN expression resulted in cell cycle arrest at G1 phase and induced apoptosis. Meanwhile, western blotting analysis showed that
EMMPRIN knockdown was associated with downregulation of cell cycle- and apoptosis-related molecules including
cyclin D1,
cyclin E, as well as increase in cleavage of
caspase-3 and PARP. This study also showed that silencing of
EMMPRIN sensitized U937 cells to
Adriamycin.
EMMPRIN is involved in proliferation, growth, and chemosensitivity of human AML line U937, indicating that
EMMPRIN may be a promising therapeutic target for AML.