Knockdown of MEF2D inhibits the development and progression of B-cell acute lymphoblastic leukemia.

BACKGROUND

Myocyte enhancer factor 2D (MEF2D) is involved in the progression of various malignant tumors. However, its impact on B-cell acute lymphoblastic leukemia (B-ALL) has not been elucidated.

METHODS

In this study, the expression level of MEF2D in B-ALL patients was validated through the Gene Expression Omnibus (GEO) database and clinical specimens. MEF2D-knockdown B-ALL cell lines were constructed by lentivirus transfection, and the effects of MEF2D on the viability, apoptosis, cycle progression, and drug sensitivity of B-ALL cells were verified by Cell Counting Kit-8 (CCK-8) and flow cytometry (FCM). The effect of MEF2D on the proliferation of B-ALL cells was verified via the construction of a xenograft mouse model. The mechanism of MEF2D regulating B-ALL cells was explored by RNA sequencing analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemical (IHC).

RESULTS

In this study, overexpression of MEF2D was observed in B-ALL patients and was remarkably correlated to disease progression in ALL patients. The knockdown of MEF2D expression suppressed cell viability, induced cell apoptosis, blockaded cell cycle progression, enhanced drug sensitivity of B-ALL cells , and reduced the tumor load . Furthermore, mechanistic studies revealed that MEF2D knockdown downregulated the expression of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT) signaling pathway.

CONCLUSIONS

Our research demonstrated that MEF2D was markedly expressed in B-ALL. MEF2D knockdown inhibited cancer progression of B-ALL both and , which may be related to the downregulation of the PI3K-AKT signaling pathway. The data suggest that MEF2D plays a vital role in the process of tumorigenesis and may be a potential novel target for B-ALL therapy.