Jichu yixue yu linchuang (Apr 2021)
Expression and function of Met-tRNAiMet carrier proteins in acute myeloid leukemia
Abstract
Objective To investigate the expression of Met-tRNAiMetcarrier proteins eIF2A, eIF2D and MCTS1 in normal hematopoietic stem cells (HSCs) and acute myeloid leukemia (AML) cells, and to study the effect of carrier proteins on the functions of AML cell lines. Methods The expression of carrier proteins among multiple stages of mouse HSCs differentiation was analyzed by public datasets. The expression of carrier proteins among multiple stages of human HSCs differentiation was analyzed in single cell RNA-sequencing datasets. The expression of carrier pro- teins among AML patients and normal was analyzed in public datasets. eIF2A or eIF2D expression was inhibited by lentivirus-mediated gene transduction in AML cell line MOLM13, cell proliferation and cell cycle was analyzed.AML cell line was treated with salubrinal (10 μmol/L) and serum starvation, which make cells in stress, and the expression of eIF2A and eIF2D were detected. Results The expression of eIF2A and eIF2D in hematopoietic stem and progenitor cells (HSPCs) was higher than mature blood cells, and in AML patients was higher than normal. On the contrary, the expression of MCTS1 had no difference in normal hematopoietic differentiation process, as well as AML vs normal. eIF2A or eIF2D knock down significantly suppressed cell proliferation (P＜0.0001), as well as caused cell cycle arrest in G2/M (P＜0.001). After MOLM13 was treated with salubrinal and serum starvation, the expression of eIF2A and eIF2D was upregulated. Conclusions eIF2A and eIF2D may regulate AML cell growth through breaking cell cycle arrest.
