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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

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dc.contributor.authorHu, Yan
dc.contributor.authorMu, Hanshuo
dc.contributor.authorYang, Ying
dc.date.accessioned2023-01-24T09:38:57Z
dc.date.available2023-01-24T09:38:57Z
dc.date.issued2021
dc.description.abstractPHD 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.es
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dc.format.extent9es
dc.identifier.citationHistology and Histopathology Vol. 36, nº8 (2021)
dc.identifier.doihttps://doi.org/10.14670/HH-18-349
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/127728
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectNSCLCes
dc.subjectPHF8es
dc.subjectWnt/β-catenin signalinges
dc.subjectMetastasises
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleHistone demethylase PHF8 promotes cell growth and metastasis of non-small-cell lung cancer through activating Wnt/β-catenin signaling pathwayes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.36, nº8 (2021)