ArticleJournal of cellular and molecular medicine2018
MYCN is a novel oncogenic target in adult B-ALL that activates the Wnt/β-catenin pathway by suppressing DKK3.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Chidamide and venetoclax synergistically regulate the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL.Annals of hematology · 2025Article
- Review
- The Wnt/β-catenin signalling pathway in Haematological Neoplasms.Biomarker research · 2022Review
- HCV Core protein represses DKK3 expression via epigenetic silencing and activates the Wnt/β-catenin signaling pathway during the progression of HCC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Identification of methylation signatures associated with CAR T cell in B-cell acute lymphoblastic leukemia and non-hodgkin's lymphoma.Frontiers in oncology · 2022Article
- MYC Hyperactivates Wnt Signaling inMolecular cancer research : MCR · 2021Article
- Histone deacetylase inhibitor chidamide regulates the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL.Investigational new drugs · 2021Article
- A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia.Journal of translational medicine · 2021Article
- The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche.Frontiers in cell and developmental biology · 2020Review
- Cell signaling and cancer: a mechanistic insight into drug resistance.Molecular biology reports · 2019Review
- Downregulation of the histone methyltransferase SETD2 promotes imatinib resistance in chronic myeloid leukaemia cells.Cell proliferation · 2019Article
- LncRNA SNHG16 promotes epithelial- mesenchymal transition via down-regulation of DKK3 in gastric cancer.Cancer biomarkers : section A of Disease markers · 2019Article
- Circular RNA regulatory network reveals cell-cell crosstalk in acute myeloid leukemia extramedullary infiltration.Journal of translational medicine · 2018Article
- MYCN is a novel oncogenic target in adult B-ALL that activates the Wnt/β-catenin pathway by suppressing DKK3.Journal of cellular and molecular medicine · 2018Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dickkopf-3 (DKK3) is frequently down-regulated by promoter hypermethylation and is closely associated with a poor prognosis in many cancers. Our previous studies have shown that miR-708 down-regulates DKK3 at the post-transcriptional level in B-ALL. However, whether transcriptional mechanisms lead to DKK3 silencing remains unclear. Here, we analysed the promoter regions of DKK3 by bioinformatics and found binding sites for MYCN. A dual-luciferase reporter gene assay and ChIP experiments revealed that MYCN negatively regulates DKK3 at the transcriptional level in B-ALL cell lines, and using bisulphite sequencing PCR, we affirmed that MYCN has no effect on the methylation of the DKK3 promoter. MYCN silencing in B-ALL cells resulted in reduced cell proliferation, increased apoptosis and G1 phase arrest. Treatment with MYCN siRNA or 5-aza-2'-deoxycytidine (5-AdC), a demethylating agent, significantly increased the levels of DKK3 mRNA and protein and decreased the protein levels of p-GSK3β and nuclear β-catenin, which indicates inhibition of the Wnt/β-catenin pathway in vitro. MYCN knockdown significantly decreased the tumorigenic capacity of Nalm6 cells, which restored DKK3 levels and inhibited the Wnt/β-catenin pathway in vivo. Our study provides an increased understanding of adult B-ALL pathogenesis, which may be beneficial to the development of effective prognostic markers or therapeutic targets.
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