Browsing by Subject "Wnt/β-catenin signaling"

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    EFNA4 deletion suppresses the migration, invasion, stemness, and angiogenesis of gastric cancer cells through the inactivation of Pygo2/Wnt signaling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Wang, Xian; Zhang, Tiran; Yu, Rong
    Gastric cancer represents an aggressive malignancy and a leading contributor to cancer death. Ephrin-A4 (EFNA4) has been proposed to be related to the immune microenvironment and prognosis of gastric cancer. This study was undertaken to discuss the participation and mechanism of EFNA4 in the development of gastric cancer. RT-qPCR and western blot examined EFNA4 and Pygopus2 (Pygo2) expression in gastric cancer cells. After transfection of EFNA4 interference plasmids or co-transfection of EFNA4 interference plasmids and Pygo2 overexpression plasmids, cell proliferation was detected by the CCK-8 method and EDU staining. Wound healing, Transwell, TUNEL, and endothelial cell tube formation assays detected cell migration, invasion, apoptosis, and angiogenesis, respectively. Western blot examined the expression of metastasis-, apoptosis-, angiogenesis-, and Wnt signaling-associated proteins. Cell stemness was estimated by the sphere formation assay, RT-qPCR, and western blot. Through the experimental data, it was noticed that EFNA4 expression was increased in gastric cancer cells. Knockdown of EFNA4 suppressed the proliferation, migration, invasion, angiogenesis as well as stemness while aggravating the apoptosis of gastric cancer cells. Also, EFNA4 depletion reduced Pygo2 protein expression and then inactivated Wnt/β-catenin signaling. Further elevation of Pygo2 reversed the impacts of EFNA4 silencing on Wnt/β-catenin signaling, cell proliferation, apoptosis, migration, invasion, angiogenesis as well as stemness in gastric cancer. Accordingly, the knockdown of EFNA4 might downregulate Pygo2 and inactivate Wnt/β-catenin signaling to exert protective effects against gastric cancer
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    Histone demethylase PHF8 promotes cell growth and metastasis of non-small-cell lung cancer through activating Wnt/β-catenin signaling pathway
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Hu, Yan; Mu, Hanshuo; Yang, Ying
    PHD finger protein 8 (PHF8), serving as a histone demethylase, is upregulated in some types of malignant tumors. The role of PHF8 in non-small-cancer lung carcinoma (NSCLC) remains unclear. This study aims to verify the effect of PHF8 in NSCLC and its molecular mechanism. We collected 20 cases of fresh NSCLC and adjacent lung tissues to assess differential expressions of PHF8 by reverse transcriptionquantitative PCR (RT-qPCR). Western blot was employed to examine protein levels of PHF8, Wnt1, βcatenin and epithelial-mesenchymal transition (EMT) related proteins. Chromatin immunoprecipitation assays were executed to confirm the regulatory mechanism of PHF8 and Wnt1. Cell Counting Kit-8 assays and Transwell assays were utilized to identify the effects of PHF8/Wnt1 pathway on cell proliferation, migration and invasion. PHF8 was overexpressed in NSCLC tissues and cells and higher PHF8 expression was correlated with poorer overall survival in NSCLC patients. PHF8 overexpression promoted NSCLC cell proliferation, migration and invasion, while PHF8 knockdown exerted the opposite effect. Mechanistic investigations identified that PHF8 occupied the Wnt1 promoter, leading to a decrease of repressive histone markers H3K9me1, H3K9me2, H3K27me2 and H4K20me1 in the promoter region of the Wnt1 gene, which further promoted the transcription of the Wnt1 gene. PHF8 activated Wnt/βcatenin signaling pathway through promoting Wnt1 expression. Besides, PHF8 altered the EMT of NSCLC through regulating Wnt1 levels. PHF8, acting as an oncogene and prognostic biomarker in NSCLC, stimulated NSCLC to proliferate, metastasis and EMT by activating Wnt/β-catenin signaling.