MiR-144 targets APP to regulate AML1/ETO+ leukemia cell migration via p-ERK/c-Myc/MMP-2 pathway
MiR-144 targets APP to regulate AML1/ETO+ leukemia cell migration via p-ERK/c-Myc/MMP-2 pathway
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MiR-144靶向APP通过p-ERK/c-Myc/MMP-2途径调节AML1/ETO白血病细胞迁移
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通讯作者：
Fanyi Meng
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作者：
Ling Jiang;Wei Meng;Guopan Yu;Changxin Yin;Zhixiang Wang;Rui Cao;Libin Liao;Zhongxin Zheng;Fanyi Meng
Extramedullary infiltration (EMI) is very common in Acute Myeloid Leukemia (AML) patients, and it is closely related with the disease prognosis. Our previous study reported that patients with AML1/ETO+ (A/E+) and expression of Amyloid Precursor Protein (APP) tended to develop EMI and carried out of poor prognosis. In this study, we found that relapse-free survival (RFS) and overall survival (OS) were significantly lower in patients with EMI than those without it. We demonstrated that EMI incidence was significantly higher (P<0.05) while RFS and OS rates were significantly lower (P<0.05) in the patients with high expressions of APP. In vitro study, we used kasumi-1 cells which carry A/E+ oncogene and APP gene as our cell model to detect the mechanisms in detail. After knockdown of APP expression, the cell migration was significantly reduced (P<0.05). Furthermore, Western-Blot showed that the protein expression of p-ERK, MMP-2 and c-Myc were significantly reduced after interference of APP, while CXCR4 and MMP-9 didn’t change. After that, we co-culture p-ERK and c-Myc inhibition with Kasumi-1 cells respectively and demonstrated that APP/p-ERK/c-Myc/MMP-2 pathway was the signal transduction in regulation of cell migration. In further, we constructed miR-144 MIMICs and transfected Kasumi-1 cells, qRT-PCR and Western-Blot showed miR-144 was negatively regulated of APP. Based on these findings, we concluded that miR-144 negatively targeted with APP gene and regulate cell migration via APP/p-ERK/c-Myc/MMP-2 pathway.
