DIXDC1 promotes the growth of acute myeloid leukemia cells by upregulating the Wnt/β-catenin signaling pathway - 20/09/18
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Graphical abstract |
Highlights |
• | DIXDC1 expression is upregulated in AML cell lines. |
• | DIXDC1 knockdown inhibits the growth of AML cells. |
• | DIXDC1 overexpression promotes the growth of AML cells. |
• | DIXDC1 is involved in regulating Wnt/β-catenin signaling. |
• | Knockdown of β-catenin reverses the oncogenic effect of DIXDC1. |
Abstract |
Accumulating evidence suggests that dysregulation of Dishevelled-Axin domain-containing 1 (DIXDC1) is involved in the progression and development of various cancers. However, little is known about the relevance of DIXDC1 in acute myeloid leukemia (AML). In this study, we aimed to investigate the expression status and potential biological function of DIXDC1 in AML. Our results showed that DIXDC1 expression was highly upregulated in AML cell lines and primary AML blasts compared with normal blasts. Knockdown of DIXDC1 by siRNA-mediated gene silencing significantly inhibited proliferation, induced cell cycle arrest, and promoted apoptosis of AML cells in vitro. By contrast, DIXDC1 overexpression promoted proliferation, accelerated cell cycle progression, and reduced apoptosis of AML cells. Moreover, we found that DIXDC1 knockdown decreased the expression of β-catenin and restricted the activation of Wnt signaling. In addition, DIXDC1 knockdown decreased the expression of Wnt/β-catenin target genes, including cyclin D1 and c-myc, while DIXDC1 overexpression had the opposite effect. Notably, β-catenin knockdown partially reversed the oncogenic effect of DIXDC1 in AML cells. Taken together, these results demonstrate that DIXDC1 promotes the growth of AML cells, possibly through upregulating the Wnt/β-catenin signaling pathway. Our study suggests that DIXDC1 may serve as a potential therapeutic target for the treatment of AML.
Le texte complet de cet article est disponible en PDF.Abbreviations : AML, DIXDC1, FBS, CCK-8, RT-qPCR
Keywords : Acute myeloid leukemia, DIXDC1, Wnt/β-catenin
Plan
Vol 107
P. 1548-1555 - novembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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