Silencing expression of PHF14 in glioblastoma promotes apoptosis, mitigates proliferation and invasiveness via Wnt signal pathway

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.

The high mobility group protein HMG20A cooperates with the histone reader PHF14 to modulate TGFβ and Hippo pathways

“…We show here that HMG20A and PHF14 share an important number of targets related to the mesenchymal phenotype of the TNBC cell line MDA-MB-231. Defects in migration and invasion due to PHF14 KD have been previously reported in glioblastoma multiforme, lung, bladder and gastric cancer cell lines ( 44 , 45 , 82 , 83 ). However, the signaling pathways involved in this regulation are unclear.…”

“…have proposed that PHF14 modulates the AKT-mTOR pathway ( 44 , 45 ), while Wu et al. reported that the Wnt signaling pathway is affected by PHF14 silencing ( 83 ). However, our results in MDA-MB-231 cells revealed that the AKT-mTOR signaling pathway was not affected by either HMG20A or PHF14 KD, and our RNA-seq transcriptomic analysis does not support the downregulation of Wnt signaling in either KD condition.…”

PHF14 Promotes Cell Proliferation and Migration through the AKT and ERK1/2 Pathways in Gastric Cancer Cells

“…Some study illustrates that PHD finger proteins generally promote proliferation and migration in cancer cells [25,37], which is also consistent with our results. A latest study indicates that silencing PHF14 induces apoptosis in glioblastoma cells [39]; however, there is no apoptosis in gastric cancer cells after knocking down of PHF14, which remind us that PHF14 plays different roles in different cancers. e different role of PHF14 may be induced by activation of different pathways.…”

Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy

“…This is a profound platform that can be utilized to analyze the current and future trends in the diagnosis and prognosis of glioma from molecular biology to proteomics. Recent studies disclosed several signal pathways that closely related to the proliferation and metastasis of glioma, such as IGF-1R/AKT, Notch, mTOR, Wnt and EMT (28)(29)(30)(31)(32). EMT is an indispensable part of the normal development process of the human body, and it also plays a crucial role in tumor progression and metastasis.…”