Abstract
BackgroundPHF21B is newly identified to be involved in the tumor progression; however, its biological role and molecular mechanism in prostate cancer have not been defined. This study is aimed to study the role of PHF21B in the progression of prostate cancer.MethodsReal-time PCR, immunohistochemistry and western blotting analysis were used to determine PHF21B expression in prostate cancer cell lines and clinical specimens. The role of PHF21B in maintaining prostate cancer stem cell-like phenotype was examined by tumor-sphere formation assay and expression levels of stem cell markers. Luciferase reporter assay, western blot analysis, enzyme-linked immunosorbent assay and ChIP assay were used to determine whether PHF21B activates the Wnt/β-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2.ResultsOur results revealed that PHF21B was markedly upregulated in prostate cancer cell lines and tissues. High PHF21B levels predicted poorer recurrence-free survival in prostate cancer patients. Gain-of-function and loss-of-function studies showed that overexpression of PHF21B enhanced, while downregulation suppressed, the cancer stem cell-like phenotype in prostate cancer cells. Xenograft tumor model showed that silencing PHF21B decreased the ability of tumorigenicity in vivo. Notably, Wnt/β-catenin signaling was hyperactivated in prostate cancer cells overexpressing PHF21B, and mediated PHF21B-induced cancer stem cell-like phenotype. Furthermore, PHF21B suppressed repressors of the Wnt/β-catenin signaling cascade, including SFRP1 and SFRP2. These results demonstrated that PHF21B constitutively activated wnt/β-catenin signaling by transcriptionally downregulating SFRP1 and SFRP2, which promotes prostate cancer stem cell-like phenotype.ConclusionsOur results revealed that PHF21B functions as an oncogene in prostate cancer, and may represent a promising prognostic biomarker and an attractive candidate for target therapy of prostate cancer.
Highlights
PHF21B is newly identified to be involved in the tumor progression; its biological role and molecular mechanism in prostate cancer have not been defined
Expression of PHF21B is upregulated in Prostate cancer (PCa) cell lines and tissues By analysis of the RNA expression data from The Cancer Genome Atlas (TCGA), we found that PHF21B levels were significantly upregulated in human PCa tissues (n = 497) compared with that in normal prostate tissues (n = 52) (P < 0.001) (Fig. 1a)
Upregulation of PHF21B correlates with progression and poor prognosis in PCa To investigate the clinical significance of upregulation of PHF21B in PCa, PHF21B protein expression was examined in 116 paraffin-embedded, archived PCa tissues using IHC
Summary
PHF21B is newly identified to be involved in the tumor progression; its biological role and molecular mechanism in prostate cancer have not been defined. This study is aimed to study the role of PHF21B in the progression of prostate cancer. For patients with advanced prostate cancer, androgen deprivation therapy (ADT) has been the standard therapy. Most patients relapse and develop castration-resistant prostate cancer within 18–24 months following ADT [5]. CSCs are responsible for tumor initiation, chemotherapy resistance and become enriched after ADT treatment, which leads to poor outcomes and recurrence in PCa patients [8,9,10,11,12,13]. Unveiling the underlying molecular mechanism of prostate CSCs turns out to be the essential and profound topic for PCa treatment
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