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

Shuai Wu; Chen Luo; Fengjiao Li; N U Farrukh Hameed; Qiuyan Jin; Jie Zhang

doi:10.1186/s12935-019-1040-6

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

Cancer Cell Int. 2019 Nov 27:19:314. doi: 10.1186/s12935-019-1040-6. eCollection 2019.

Authors

Shuai Wu¹, Chen Luo^{1

2}, Fengjiao Li², N U Farrukh Hameed¹, Qiuyan Jin², Jie Zhang¹

Affiliations

¹ 1Glioma Surgery Division, Neurologic Surgery Department, Huashan Hospital, Fudan University, Shanghai, 200040 China.
² 2Department of Human Anatomy and Histoembryology, Fudan University, Shanghai, 200433 China.

Abstract

Background: The 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).

Methods: Tissue 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.

Results: Our 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.

Conclusions: Our data provide a new insight into the biological significance of PHF14 in glioma and its potential application in therapy and diagnosis.

Keywords: Apoptosis; GBM; Invasiveness; PHF14; Proliferation.