Open Access

ARTICLE

Knockdown of IARS2 Inhibited Proliferation of Acute Myeloid Leukemia Cells by Regulating p53/p21/PCNA/eIF4E Pathway

Hong Li^*1, Yaning Tian^*1, Xiang Li^*, Bin Wang^†, Dongzhi Zhai^*, Yingying Bai^*, Changhu Dong^*, Xu Chao^*‡

* The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, P.R. China
† The College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, P.R. China
‡ The College of Preclinical Sciences, Shaanxi University of Chinese Medicine, Xianyang, P.R. China

Oncology Research 2019, 27(6), 673-680. https://doi.org/10.3727/096504018X15426261956343

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.

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