EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β‐catenin at Ser552

Zhu, Xiao-Xu; Li, Jianhui; Cai, Jinhua; Xu, Hongguo; Huang, Chen‐Song; Huang, Xi‐Tai; Wang, Jie‐Qin; Li, Shijin; Xu, Qiong‐Cong

doi:10.1111/cas.14159

Cited by 13 publications

(7 citation statements)

References 27 publications

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“…In consistent with this experimental study, expression profile analysis indicated that high SIX3 mRNA level was a protective factor for OS and RFS of basal-like breast cancer patients [24]. Several studies proved that EYA4 behaved as a tumor suppressor and associated with favorite prognosis in hepatocellular carcinoma and pancreatic ductal adenocarcinoma [25,26]. In summary, multiple studies suggested that members of RDGN family played distinct roles depending on the cancer type.…”

Section: Open Accesssupporting

confidence: 83%

RDGN-based predictive model for the prognosis of breast cancer

Dong

Luo

et al. 2020

Exp Hematol Oncol

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Background: Breast cancer is the most diagnosed malignancy in females in the United States. The members of retinal determination gene network (RDGN) including DACH, EYA, as well as SIX families participate in the proliferation, apoptosis, and metastasis of multiple tumors including breast cancer. A comprehensive predictive model of RDGN might be helpful to herald the prognosis of breast cancer patients. Methods: In this study, the Gene Expression Ominibus (GEO) and Gene Set Expression Analysis (GSEA) algorithm were used to investigate the effect of RDGN members on downstream signaling pathways. Besides, based on The Cancer Genome Atlas (TCGA) database, we explored the expression patterns of RDGN members in tumors, normal tissues, and different breast cancer subtypes. Moreover, we estimated the relationship between RDGN members and the outcomes of breast cancer patients. Lastly, we constructed a RDGN-based predictive model by Cox proportional hazard regression and verified the model in two separate GEO datasets. Results: The results of GSEA showed that the expression of DACH1 was negatively correlated with cell cycle and DNA replication pathways. On the contrary, the levels of EYA2 and SIX1 were significantly positively correlated with DNA replication, mTOR, and Wnt pathways. Further investigation in TCGA database indicated that DACH1 expression was lower in breast cancers especially basal-like subtype. In the meanwhile, SIX1 was remarkably upregulated in breast cancers while EYA2 level was increased in Basal-like and Her-2 enriched subtypes. Survival analyses demonstrated that DACH1 was a favorable factor while EYA2 and SIX1 were risk factors for breast cancer patients. Given the results of Cox proportional hazard regression analysis, two members of RDGN were involved in the present predictive model and patients with high model index had poorer outcomes. Conclusion: This study showed that aberrant RDGN expression was an unfavorable factor for breast cancer. This RDGN-based comprehensively framework was meaningful for predicting the prognosis of breast cancer patients.

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Section: Open Accesssupporting

confidence: 83%

RDGN-based predictive model for the prognosis of breast cancer

Dong

Luo

et al. 2020

Exp Hematol Oncol

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“…The consequence of the existence of EYA4 expression conceivably blocks the development of colon cancer [ 31 ], through the downregulation of MYCBP [ 48 ] via dephosphorylating β -catenin [ 49 ]. Therefore, the depletion of EYA4 expression has been detected in colorectal cancer, possibly due to hypermethylated promoter [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

Almutairi

Alrefaei

et al. 2022

BioMed Research International

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Cigarette SMOKE (CS) considerably contributes to causing some diseases such as cancer, and it has a role in the alternation of gene expression through several mechanisms including epigenetics modification, particularly DNA methylation. EYA4 is one of the genes, that whose expression has been dysregulated in lung, colon, bladder, and breast cancer, leading to tumor progression. The alternation of DNA methylation levels has been implicated in regulating the expression of the EYA4 gene. Thus, in this study, we have shown the effect of CS on the DNA methylation level of the EYA4 promoter region as well as the methylation level on EYA4 expression. To determine the level of DNA methylation on the promoter region of the EYA4 gene, we have employed the bisulfite conversion treatment followed by the Sanger Sequence for 100 DNA samples taken from Saudi people (50 smokers and 50 nonsmokers). We found that 26% of DNA extracted from smoker samples is methylated, while there was no methylation identified in nonsmoker samples. Also, using the demethylating agents such as AZA on LoVo and Caco-2 cancer cell lines causes induction of transcription level of EYA4, implying the possible mechanism of DNA methylation in the upregulation of EYA4. These findings suggest the possible mechanism of CS in controlling the expression of EYA4 via changing the status of DNA methylation.

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“…To ascertain whether avasimibe exerts its protective effect on the epithelial barrier by targeting the Wnt/β-catenin signaling pathway, we detected β-catenin-related phosphorylation sites. Previous studies have shown that these phosphorylation sites contribute to β-catenin localization at the cytomembrane, stabilization at the cytoplasm and increase cell proliferation (Ponce et al, 2011;Groulx et al, 2014;Zhu et al, 2019;Behrouj et al, 2021). Interestingly, avasimibe repressed phospho-β-catenin at Ser552, Ser675, and Thr41/Ser45 and also reduced active β-catenin levels, which could repress the Wnt/β-catenin activity (Figure 6A).…”

Section: Avasimibe Lowered Proliferation Of Basal Cells By Suppressin...mentioning

confidence: 71%

Avasimibe Alleviates Disruption of the Airway Epithelial Barrier by Suppressing the Wnt/β-Catenin Signaling Pathway

et al. 2022

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Avasimibe (Ava) is an acetyl-CoA acetyltransferase 1 (ACAT1) specific inhibitor and an established medicine for atherosclerosis, owing to its excellent and safe anti-inflammation effects in humans. However, its efficacy in asthma has not yet been reported. We first administered varying concentrations of avasimibe to house dust mite (HDM)-induced asthmatic mice; results showed that 20 mg/kg avasimibe most significantly reduced IL-4 and IL-5 production in bronchoalveolar lavage fluid (BALF) and total IgE in serum, and the avasimibe treatment also exhibited lower mucus secretion, decreased goblet and basal cells but increased ciliated cells compared to the HDM group. And the redistribution of adherens junction (AJ) proteins induced by HDM was far more less upon avasimibe administration. However, avasimibe did not reduce the cholesterol ester ratio in lung tissues or intracellular cholesterol ester, which is avasimibe’s main effect. Further analysis confirmed that avasimibe impaired epithelial basal cell proliferation independent of regulating cholesterol metabolism and we analyzed datasets using the Gene Expression Omnibus (GEO) database and then found that the KRT5 gene (basal cell marker) expression is correlated with the β-catenin gene. Moreover, we found that β-catenin localized in cytomembrane upon avasimibe treatment. Avasimibe also reduced β-catenin phosphorylation in the cytoplasm and inactivated the Wnt/β-catenin signaling pathway induced by HDMs, thereby alleviating the airway epithelial barrier disruption. Taken together, these findings indicated that avasimibe has potential as a new therapeutic option for allergic asthma.

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EYA4 inhibits hepatocellular carcinoma by repressing MYCBP by dephosphorylating β‐catenin at Ser552

Cited by 13 publications

References 27 publications

RDGN-based predictive model for the prognosis of breast cancer

RDGN-based predictive model for the prognosis of breast cancer

Cigarette Smoke Regulates the Expression of EYA4 via Alternation of DNA Methylation Status

Avasimibe Alleviates Disruption of the Airway Epithelial Barrier by Suppressing the Wnt/β-Catenin Signaling Pathway

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