@Article{096504018X15426261956343,
AUTHOR = {Hong Li,
Yaning Tian,
Xiang Li, Bin Wang, Dongzhi Zhai, Yingying Bai,
Changhu Dong, Xu Chao‡},
TITLE = {Knockdown of IARS2 Inhibited Proliferation of Acute Myeloid Leukemia Cells by Regulating p53/p21/PCNA/eIF4E Pathway},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {6},
PAGES = {673--680},
URL = {http://www.techscience.com/or/v27n6/48584},
ISSN = {1555-3906},
ABSTRACT = {IARS2 encodes mitochondrial isoleucine-tRNA synthetase, which mutation may cause multiple diseases.
However, the biological function of IARS2 on acute myeloid leukemia (AML) has not yet been identified.
In the present study, qRT-PCR was used to determine the expression of IARS2 in K562, THP1, and HL-60
leukemia cells. Additionally the mRNA levels of IARS2 in CD34 cells and AML cells obtained from patients
were detected by qRT-PCR. IARS2-shRNA lentiviral vector was established and used to infect acute myeloid
leukemia HL-60 cells. qRT-PCR and Western blot analysis were employed to assess the knockdown effect of
IARS2. The proliferation rate and cell cycle phase of HL-60 cells after IARS2 knockdown were evaluated by
CCK-8 assay and flow cytometry. The PathScan Antibody Array was used to determine the expression of cell
cycle-related proteins in HL-60 cells after IARS2 knockdown. The expression of proliferation-related proteins
in HL-60 cells after IARS2 knockdown was determined by Western blot analysis. Results showed that IARS2
expression was stable and much higher in HL-60, THP-1, and K562 leukemia cells and AML cells obtained
from patients than that of human CD34 cells. Compared with cells of the shCtrl group, IARS2 was markedly knocked down in cells that were transfected with lentivirus encoding shRNA of IARS2 in HL-60 cells
(p<0.05). IARS2 knockdown significantly inhibited the proliferation and induced cycle arrest at the G1 phase
in HL-60 cells. Additionally IARS2 knockdown significantly increased the expression of p53 and p21, and
decreased the expression of PCNA and eIF4E in HL-60 cells. In conclusion, IARS2 knockdown can inhibit
acute myeloid leukemia HL-60 cell proliferation and cause cell cycle arrest at the G1 phase by regulating the
p53/p21/PCNA/eIF4E pathways.},
DOI = {10.3727/096504018X15426261956343}
}