Eukaryotic initiation factor-2, gamma subunit, suppresses proliferation and regulates the cell cycle via the MAPK/ERK signaling pathway in acute myeloid leukemia

Abstract

Purpose The expression of eukaryotic translation initiation factor 2 subunit 3 (EIF2S3) in patients with non-small cell lung and colorectal cancer is lower than that in healthy individuals. However, the functions of EIF2S3 remain unclear, and its study in leukemia has not been reported. The article aims to explore the role of EIF2S3 in AML (acute myeloid leukemia) and its underlying mechanism.Methods Reverse transcription-quantitative PCR was performed to evaluate the expression levels of EIF2S3, and its association with patient prognosis was determined. Inducible HEL-EIF2S3 and HL-60-EIF2S3 cell lines were established by retrovirus infection. Cellular proliferation and the cell cycle were analyzed using Cell Counting Kit 8 and ow cytometric analyses. Tumorigenic ability was evaluated using xenograft nude mouse model. Gene expression pro les were analyzed in HL-60-EIF2S3 cells by next-generation sequencing, and WB analysis was performed to detect the expression of related proteins. ResultsThe expression of EIF2S3 in patients with AML was lower than that experiencing CR (P=0.02). Furthermore, EIF2S3 overexpression inhibited cellular proliferation, halted G0/1 to S phase cell cycle progression and inhibited tumorigenicity (P=0.015). 479 differentially expressed genes were identi ed between HL60-EIF2S3 DOX (-) and HL60-EIF2S3 DOX (+) cells via NGS and several of them involved in MAPK/ERK signaling pathway. The phosphorylation levels of ERK decreased when EIF2S3 was overexpressed(P 0.050).Conclusion EIF2S3 overexpression may result in a decrease in cellular proliferation, cell cycle arrest and tumorigenic inhibition via the MAPK/ERK signaling pathway in AML cells.

NCAPG2 Maintains Cancer Stemness and Promotes Erlotinib Resistance in Lung Adenocarcinoma

“…Additionally, one of the characteristics of DTP is the presence of low levels of mRNA translation [ 29 ]. EIF2S3 is a subunit of eukaryotic initiation factor 2 (eIF2) and is involved in the initiation of protein synthesis [ 30 ]. We suggest that cells could adapt to DTP by reducing the expression of EIF2S3 at the beginning of drug treatment, possibly reducing the ability of the cells to synthesize specific proteins.…”

Developmental programming: adverse sexually dimorphic transcriptional programming of gestational testosterone excess in cardiac left ventricle of fetal sheep

“…Consistent with findings of Locatelli et al 42 we also noted differential expression of gene sets associated with cellular metabolism and processes 42 . For instance, EIF2S3 gene located on X chromosomes and TP53 gene differentially expressed in female LV are involved in cell cycle activity 43 , 44 . SHROOM 2 , a gene differentially expressed in male LV in the current study, is noted to be involved in tissue morphogenesis including vascular development during fetal life 45 .…”