Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

Li, Guo; Wang, Xiaohong; Yang, Yilin; Xu, Haiwen; Yin, Lili; Wang, Yan; Mi, Yang; Song, Zhao; Bai, Song; Zhao, Ling; Wang, Zhipeng; Lian, Xin; Liu, Ying; Zhang, Qingyuan

doi:10.3892/ol.2017.7633

Cited by 6 publications

(11 citation statements)

References 32 publications

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“…In contrast, Moonlight identified SOX7, CYP26B1, DACT2 as tumor suppressors with low expression in these same cell lines. These findings were also supported by literature 22,73–75 .…”

Section: Resultssupporting

confidence: 89%

Interpreting pathways to discover cancer driver genes with Moonlight

et al. 2020

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Cancer driver gene alterations influence cancer development, occurring in oncogenes, tumor suppressors, and dual role genes. Discovering dual role cancer genes is difficult because of their elusive context-dependent behavior. We define oncogenic mediators as genes controlling biological processes. With them, we classify cancer driver genes, unveiling their roles in cancer mechanisms. To this end, we present Moonlight, a tool that incorporates multiple -omics data to identify critical cancer driver genes. With Moonlight, we analyze 8000+ tumor samples from 18 cancer types, discovering 3310 oncogenic mediators, 151 having dual roles. By incorporating additional data (amplification, mutation, DNA methylation, chromatin accessibility), we reveal 1000+ cancer driver genes, corroborating known molecular mechanisms. Additionally, we confirm critical cancer driver genes by analysing cell-line datasets. We discover inactivation of tumor suppressors in intron regions and that tissue type and subtype indicate dual role status. These findings help explain tumor heterogeneity and could guide therapeutic decisions.

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“…In contrast, Moonlight identified SOX7, CYP26B1, DACT2 as tumor suppressors with low expression in these same cell lines. These findings were also supported by literature 22,73–75 .…”

Section: Resultssupporting

confidence: 89%

Interpreting pathways to discover cancer driver genes with Moonlight

et al. 2020

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“…miRNA negative primer and U6 forward primer were provided by the miRNA First Strand cDNA Synthesis (Tailing Reaction) kit, and other primers were synthetized by Sangon ( Table S1 ). 47 , 48 , 49 …”

Section: Methodsmentioning

confidence: 99%

miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

Wang

Cen

Yang

et al. 2021

Molecular Therapy - Nucleic Acids

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Papillary thyroid cancer (PTC) is the most common type of thyroid cancer, and angiogenesis plays critical roles in its recurrence and metastasis. In this study, we investigated the effects of hypoxia-induced exosomal microRNA-181 (miR-181a) from PTC on tumor growth and angiogenesis. Thyroid-cancer-related differentially expressed miR-181a was identified by microarray-based analysis in the Gene Expression Omnibus (GEO) database. We validated that miR-181a was highly expressed in PTC cells and even more so in cells cultured under hypoxic conditions, which also augmented exosome secretion from PTC cells. Exosomes extracted from PTC cells with manipulated miR-181a and mixed-lineage leukemia 3 (MLL3) were subjected to normoxic or hypoxic conditions. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-181a inhibitor/mimic or small interfering RNA (siRNA)-MLL3 or treated with exosomes from hypoxic PTC cells. Hypoxic exosomal miR-181a delivery promoted proliferation and capillary-like network formation in HUVECs. Mechanistically, miR-181a targeted and inhibited MLL3. Furthermore, miR-181a downregulated DACT2 and upregulated YAP and vascular endothelial growth factor (VEGF). Further, hypoxic exosomal miR-181a induced angiogenesis and tumor growth in vivo , which was reversed by hypoxic exosomal miR-181a inhibitor. In conclusion, exosomal miR-181a from hypoxic PTC cells promotes tumor angiogenesis and growth through MLL3 and DACT2 downregulation, as well as VEGF upregulation.

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“…DACT2 acts as a tumour suppressor by inhibiting canonical WNT signalling and is frequently silenced by promoter hypermethylation in BC. Overexpression of DACT2 inhibited the expression of β-catenin target genes associated with tumour growth and metastasis 60 , 61 . Although these 3 genes were known to be frequently methylated in breast tumour tissues, their methylation status in circulating DNA remained unknown.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of plasma biomarkers for diagnosis of breast cancer in South Asian women

Rajkumar

Sathyanarayanan

Sridevi

et al. 2022

Sci Rep

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Breast cancer is the most common malignancy among women globally. Development of a reliable plasma biomarker panel might serve as a non-invasive and cost-effective means for population-based screening of the disease. Transcriptomic profiling of breast tumour, paired normal and apparently normal tissues, followed by validation of the shortlisted genes using TaqMan® Low density arrays and Quantitative real-time PCR was performed in South Asian women. Fifteen candidate protein markers and 3 candidate epigenetic markers were validated first in primary breast tumours and then in plasma samples of cases [N = 202 invasive, 16 DCIS] and controls [N = 203 healthy, 37 benign] using antibody array and methylation specific PCR. Diagnostic efficiency of single and combined markers was assessed. Combination of 6 protein markers (Adipsin, Leptin, Syndecan-1, Basic fibroblast growth factor, Interleukin 17B and Dickopff-3) resulted in 65% sensitivity and 80% specificity in detecting breast cancer. Multivariate diagnostic analysis of methylation status of SOSTDC1, DACT2, WIF1 showed 100% sensitivity and up to 91% specificity in discriminating BC from benign and controls. Hence, combination of SOSTDC1, DACT2 and WIF1 was effective in differentiating breast cancer [non-invasive and invasive] from benign diseases of the breast and healthy individuals and could help as a complementary diagnostic tool for breast cancer.

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Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

Cited by 6 publications

References 32 publications

Interpreting pathways to discover cancer driver genes with Moonlight

Interpreting pathways to discover cancer driver genes with Moonlight

miR-181a, delivered by hypoxic PTC-secreted exosomes, inhibits DACT2 by downregulating MLL3, leading to YAP-VEGF-mediated angiogenesis

Identification and validation of plasma biomarkers for diagnosis of breast cancer in South Asian women

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