Abstract
BackgroundThe plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families. Abnormal expression of PHF14 has been identified in various cancers and is known to be implicated in the pathogenesis of tumors. This study investigates the role and the underlying mechanisms of PHF14 in GBM (glioblastoma multiforme).MethodsTissue microarrays and public databases interrogation were used to explore the relationship between the expression of PHF14 and GBM. Three stable PHF14-silenced cell lines (U251, U87MG and A172) were constructed to assess the biological functions changes of GBM cells in vitro. In addition, tumorigenicity in vivo was also performed using U87MG cell line. To understand the mechanism of action of PHF14, RNA-Seq, qRT-PCR, Western blot, IC50 assay and subsequent pathway analysis were performed.ResultsOur results showed that the expression of PHF14 was upregulated in glioma, especially in GBM. Overexpression of PHF14 translated to poor prognosis in glioma patients. In vitro assays revealed that silencing expression of PHF14 in glioma cells inhibited migration, invasiveness and proliferation and promoted cell apoptosis. Animal assay further confirmed that over-expression of PHF14 was a dismal prognostic factor. Analysis based on RNA-Seq suggested a PHF14-dependent regulation of Wnt signaling networks, which was further validated by qRT-PCR, Western blot and IC50 analysis. In addition, the mRNA expression of several key markers of EMT (epithelial–mesenchymal transition) and angiogenesis was found to change upon PHF14 silencing.ConclusionsOur data provide a new insight into the biological significance of PHF14 in glioma and its potential application in therapy and diagnosis.
Highlights
The plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families
plant homeodomain finger protein 14 (PHF14) is overexpressed in Glioblastoma multiforme (GBM) and upregulation of PHF14 is associated with poor prognosis PHF14 is expressed both in nucleus and cytoplasm in U251 cells (Fig. 1a)
By performing immunohistochemistry on three tissue microarrays, we found a positive correlation between glioma grade and the staining intensity of PHF14 (Fig. 1b, c)
Summary
The plant homeodomain (PHD) finger protein 14 (PHF14) is a vital member of PHD finger protein families. This study investigates the role and the underlying mechanisms of PHF14 in GBM (glioblastoma multiforme). The mechanisms underlying the pathogenesis of GBM are complex, The Plant Homeodomain (PHD) finger is a protein motif capable of epigenetic regulation via reading histones states [8]. PHD finger plays a key role in the recognition and translation of histone modification marks primarily by differentially recognizing methylated [9, 10] or unmodified [11, 12] lysine, directly contributing to gene transcription activation and silencing. The dysregulation of PHD finger family proteins (PHF) (e.g., PHF1, PHF6, PHF3, PHF10 and PHF11) can result in. The PHD finger family is closely associated with GBM. The role of PHF14 remains to be explored in glioma
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