Publication: Histone demethylase PHF8 promotes cell growth and metastasis of non-small-cell lung cancer through activating Wnt/β-catenin signaling pathway
Authors
Hu, Yan ; Mu, Hanshuo ; Yang, Ying
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-349
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info:eu-repo/semantics/article
Description
Abstract
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.
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Citation
Histology and Histopathology Vol. 36, nº8 (2021)
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