STMN1 promotes the proliferation and inhibits the apoptosis of acute myeloid leukemiacells by activating the PI3K/Akt pathway

[摘要] Recent studies have shown that the microtubule disrupting protein Stathmin 1 (STMN1) is differentiallyexpressed in AML patients and healthy control. The aim of this study was to explore the effects and molecularmechanism of STMN1 in AML. Here, the expression of STMN1 in peripheral blood cells (PBMCs) and bone marrowof AML patients and healthy volunteers was detected by RT-PCR and Western blot. STMN1 expression was regulatedby transfected with STMN1 overexpressed plasmid or shRNA in two human leukemia cell lines K562 and HL60. Cellproliferation was examined by CCK8 and Edu staining. Annexin V and TUNEL assays were applied to test cellapoptosis. Flow cytometry was used to test the cell cycle distribution. The activation of the PI3K signaling pathwayand the expression levels of cell cycle and cell apoptosis-related protein were determined by Western blot. In thisstudy, we found that STMN1 was overexpressed in PBMCs and bone marrow of AML patients. STMN1 expressionwas closely related to FAB subtypes, risk stratification, disease-free survival, and overall survival of AML. Functionalassays showed that overexpression of STMN1 in HL60 and K562 cells enhanced cell proliferation, decreased cellapoptosis, and caused G1 phase arrest. In contrast, suppression of STMN1reduced cell proliferation and enhanced cellapoptosis in both HL60 and K562 cells. Moreover, the PI3K/Akt pathway was activated by STMN1, while suppressionof STMN1 dysregulated the PI3K/Akt pathway and upregulating the levels of caspases3 and Bax expression. Inconclusion, STMN1 was confirmed to promote the proliferation and inhibit the apoptosis of HL60 and K562 cells bymodulating the PI3K/Akt pathway. STMN1 might be a novel molecular target for treating AML.

[学科分类] 仪器

[关键词] STMN1;AML;PI3K/Akt