OBJECTIVE: Previous studies have shown that glycosylphosphatidylinositol Anchor Attachment Protein 1 (GPAA1) is a cancer-promoting gene; however, the role of GPAA1 in childhood acute lymphoblastic leukemia (ALL) has not been reported. This study aims to illustrate the role of GPAA1 in promoting the metastasis of ALL by targeting c-myc and the potential mechanism.
PATIENTS AND METHODS: Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to examine serum levels of GPAA1 and c-myc in 42 childhood ALL patients and healthy volunteers. The interaction between GPAA1 expression and prognosis of childhood ALL was analyzed. Meanwhile, expressions of GPAA1 and c-myc in ALL cell lines were determined by qRT-PCR. Furthermore, after GPAA1 knockdown model was constructed by lentivirus transfection in MOLT-4 and SUP-B15 cells, cell counting kit-8 (CCK-8), transwell invasion, and cell wound healing assays were conducted to analyze the effect of GPAA1 on the biological functions of ALL cells. Potential mechanism was further explored through Luciferase reporter gene assay and cell recovery experiments.
RESULTS: QRT-PCR results indicated that serum level of GPAA1 in childhood ALL patients was remarkably higher than that of healthy volunteers, and the difference was statistically significant. Childhood ALL patients with high expression of GPAA1 had lower overall survival rate compared with those expressing low expression of GPAA1. Proliferation and metastasis abilities of pediatric ALL cells with GPAA1 knockdown remarkably decreased. Subsequently, c-myc expression was also found remarkably upregulated in ALL cell lines and serum samples of childhood ALL patients and it was positively correlated with GPAA1 level. In addition, Luciferase reporter gene assay demonstrated that overexpression of c-myc remarkably attenuated the Luciferase activity of the wild-type GPAA1 vector without attenuating that of the mutant vector or empty vector, further demonstrating that GPAA1 can be targeted by c-myc. At the same time, cell recovery experiment found that the interaction between GPAA1 and c-myc together regulated the malignant progression of ALL.
CONCLUSIONS: GPAA1 was up-regulated in serum of childhood ALL patients, which was remarkably associated with the prognosis. In addition, GPAA1 may contribute to the malignant progression of childhood ALL via activating c-myc.Free PDF Download
To cite this article
J.-X. Zhang, J.-H. Wang, X.-G. Sun, T.-Z. Hou
GPAA1 promotes progression of childhood acute lymphoblastic leukemia through regulating c-myc
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 9