PHF21B overexpression promotes cancer stem cell-like traits in prostate cancer cells by activating the Wnt/β-catenin signaling pathway

Background: phf21b 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. methods: real-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. results: our 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. conclusions: our 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. © 2017 the author(s).