Research Article: Dickkopf 2 serves as a novel therapeutic target and prognostic biomarker in acute myeloid leukemia targeted by evodiamine
Abstract:
Acute myeloid leukemia (AML) has seen a significant increase in cases recently, often leading to a poor outlook. Dysregulated cell death is a characteristic of AML that aids in both the formation and advancement of the disease. Dickkopf 2 (DKK2) is known to promote tumorigenesis and metastasis through multiple mechanisms, facilitating cancer development and progression. The specific function of DKK2 in AML is not yet completely understood.
The potential of DKK2 as a prognostic marker in AML was assessed using data from the Gene Expression Omnibus (GEO; accession number GSE26294) and The Cancer Genome Atlas (TCGA). Cell growth, proliferation, apoptosis, and migration were assessed following the upregulation or downregulation of DKK2 in AML cells using CCK-8, EdU staining, AO/EB staining, and transwell assays. Furthermore, molecular docking and dynamics simulations were performed to predict the interaction and binding affinity between DKK2 and evodiamine. Rescue experiments were further conducted to elucidate the functional relationship between DKK2 and evodiamine.
In AML, DKK2 expression was notably increased and linked to poor overall survival. Reducing DKK2 levels hindered AML cell growth, proliferation, and migration, while promoting apoptosis. Conversely, overexpression of DKK2 promoted the malignant phenotype of AML cells. Additionally, evodiamine was identified as a potential small-molecule compound that may functionally regulate DKK2 in AML evodiamine showed a strong binding affinity to DKK2, with a binding energy measured at ?5.51?kcal/mol. Importantly, the overexpression of DKK2 negated the anti-cancer effects of evodiamine in AML cells.
The DKK2/evodiamine axis represents a novel prognostic biomarker and a promising therapeutic target for AML.
Introduction:
AML is a condition marked by the unchecked growth of myeloid cells and an interruption in their maturation ( 1 , 2 ). It is the most prevalent type of acute leukemia in adults and is linked to a serious clinical progression ( 3 , 4 ). Although there have been advancements in diagnosing and treating AML, the overall survival rate is still low, with a 5-year survival rate that remains disappointingly low ( 5 , 6 ). This is primarily due to the fact that high relapse rates and disease progression represent major…
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