Downregulation of serum DKK-1 predicts poor prognosis in patients with papillary thyroid cancer

Zhao, Yujie; Wang, W; Wang, X H; Xu, Yi; Wang, Y; Dong, Zhihong; Zhang, J J

doi:10.4238/2015.december.28.38

Cited by 11 publications

(9 citation statements)

References 24 publications

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“…However, how cancer cells evade negative regulation of Wnt/ β -catenin signaling and establish constitutive β -catenin/TCF activation remains unclear. Most importantly, our results established DKK1, a negative regulator of Wnt signaling, as a direct functional effector of miR-373-3p in TSCC, which is in agreement with many studies showing that DKK1 is downregulated in various cancers [30–32]. So far, how DKK1 functions and regulates in TSCC remains unclear.…”

Section: Discussionsupporting

confidence: 91%

miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma

Weng

Zhang

Wang

et al. 2017

BioMed Research International

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MicroRNAs (miRNAs) regulate gene expression and at the same time mediate tumorigenesis. miR-373-3p has diverse effects in tumors, but its role in tongue squamous cell carcinoma (TSCC) remains unknown. The purpose of this study is to determine the function of miR-373-3p in the progression of TSCC. Our results brought to light that miR-373-3p is markedly upregulated in clinical TSCC tissues compared with paired adjacent normal tissues and has significant correlation with a more aggressive TSCC phenotype in patients. Gain-of-function and loss-of-function studies revealed that ectopic miR-373-3p overexpression promoted the metastasis of TSCC cells. Notably, Wnt/β-catenin signaling was hyperactivated in TSCC cells overexpressing miR-373-3p, and this pathway was responsible for the epithelial-mesenchymal transition (EMT) induced by miR-373-3p. Furthermore, miR-373-3p directly targeted and suppressed Dickkopf-1 (DKK1), a negative regulator of the Wnt/β-catenin signaling cascade. These results demonstrate that, by directly targeting DKK1, miR-373-3p constitutively activated Wnt/β-catenin signaling, thus promoting the EMT-induced metastasis of TSCC. Taken together, our findings reveal a new regulatory mechanism for miR-373-3p and suggest that miR-373-3p might be a potential target in TSCC therapy.

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Section: Discussionsupporting

confidence: 91%

miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma

Weng

Zhang

Wang

et al. 2017

BioMed Research International

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“…However, it was reported that DKK1 inhibited the survival and migration of TC cells by repressing Wnt/β‐catenin signaling pathway 41 . Downregulation of DKK1 prediected poor prognosis in thyroid cancer 42 . These results were consistent with our study.…”

Section: Discussionsupporting

confidence: 92%

M2‐like tumor‐associated macrophages‐secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β‐catenin pathway in thyroid cancer

Feng

Chen

et al. 2020

Molecular Carcinogenesis

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BackgroundThyroid carcinoma (TC) has been a global issue for its rapid increasing incidence worldwide. Although most TC was not so aggressive with a good prognosis, treatment against anaplastic TC was relatively limited and the mechanisms are not well elucidated yet.MethodsTC cell lines (IHH4 and TPC‐1) were used. Flow cytometry was used to identify the surface marker of M2‐like tumor‐associated macrophages (TAMs) from cell culture. Quantitative real‐time polymerase chain reaction, western blot analysis, immunostaining, and immunohistochemistry were used to detect the expression of Wnt1, Wnt3a, components of Wnt/β‐catenin pathway, and proliferation/epithelial–mesenchymal transition (EMT)‐related proteins. Alkaline phosphatase activity assay, colony formation assay, and transwell assay were used to examine the roles of Wnt1, Wnt3a, and β‐catenin pathway in cell dedifferentiation, proliferation, migration, and invasion of TC cells, respectively. Subcutaneous tumor growth was monitored in nude mice.ResultsCoculture with M2‐like TAMs facilitated dedifferentiation, proliferation, migration, and invasion in TC cells. EMT and proliferation‐related proteins were also promoted in cocultured TC cells. The level of Wnt1 and Wnt3a was increased in the coculture system. Block of Wnt1 or Wnt3a suppressed malignant behaviors in cocultured tumor cells. Furthermore, Wnt1 or Wnt3a knockdown inhibited Wnt/β‐catenin signaling pathway, and suppressed EMT and proliferation‐related signals in cocultured tumor cells. Knockdown of Wnt1 or Wnt3a inhibited tumor growth in xenograft model.ConclusionM2‐like TAMs promoted dedifferentiation, proliferation, and metastasis of TC by Wnt1 and Wnt3a secretion and ensuing β‐catenin activation.

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“…DKK2 generally acts as a negative regulator of canonical WNT signaling, depending on the cellular context 47 . A related family member, DKK1, has been shown to inhibit thyroid cancer survival 48 and its downregulation correlates with poorer prognosis in PTC 49 . Furthermore, we also observed significant upregulation of EGFR upon knockdown of EPB41L4A.…”

Section: Discussionmentioning

confidence: 99%

Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma

Comiskey

Liyanarachchi

et al. 2020

Sci Rep

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Papillary thyroid carcinoma (PTC) is the most common histotype of thyroid carcinoma. The heritability of PTC is high compared to other cancers, but its underlying causes are unknown. A recent genome-wide association study revealed the association of a variant at the 5q22 locus, rs73227498, with PTC predisposition. We report that rs17134155, a variant in high linkage disequilibrium with rs73227498, is located in an enhancer region downstream of coding transcripts of EPB41L4A. Rs17134155 showed significant enhancer activity in luciferase assays, and haplotypes containing the protective allele of this variant conferred a significantly lower risk of PTC. While the index SNP, rs73227498, acted as a significant cis-eQTL for expression of EPB41L4A, rs17134155 was a significant cis-sQTL for the alternative splicing of a non-coding transcript of EPB41L4A, called EPB41L4A-203. We also performed knockdown of EPB41L4A followed by microarray analysis. Some of the top differentially-expressed genes were represented among regulators of the WNT/β-catenin signaling pathway. Our results indicate that an enhancer region at 5q22 regulates the expression and splicing of EPB41L4A transcripts. We also provide evidence that EPB41L4A expression is involved in regulating growth and differentiation pathways, suggesting that decreased expression of EPB41L4A is a mechanism in the predisposition to PTC.

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Downregulation of serum DKK-1 predicts poor prognosis in patients with papillary thyroid cancer

Cited by 11 publications

References 24 publications

miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma

miR-373-3p Targets DKK1 to Promote EMT-Induced Metastasis via the Wnt/β-Catenin Pathway in Tongue Squamous Cell Carcinoma

M2‐like tumor‐associated macrophages‐secreted Wnt1 and Wnt3a promotes dedifferentiation and metastasis via activating β‐catenin pathway in thyroid cancer

Characterizing the function of EPB41L4A in the predisposition to papillary thyroid carcinoma

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