Elevated expression of ZNF217 promotes prostate cancer growth by restraining ferroportin-conducted iron egress
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Xingkang Jiang1, Changwen Zhang1, Shiyong Qi1, Shanqi Guo2, Yue Chen1, E Du1, Hongtuan Zhang1, Xiaoming Wang1, Ranlu Liu1, Baomin Qiao1, Kuo Yang1, Zhihong Zhang1, Yong Xu1
1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin 300211, China
2Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300112, China
Yong Xu, email: [email protected]
Zhihong Zhang, email: [email protected]
Keywords: ferroportin, prostate cancer, MAZ, EZH2, ZNF217
Abbreviations: Prostate cancer (PCa); Zinc-figure protein 217 (ZNF217); reverse transcription and quantitative real-time PCR analysis (qRT-PCR); Chromatin imunoprecipitation (ChIP); Ferroportin (FPN)
Received: August 20, 2016 Accepted: October 05, 2016 Published: October 19, 2016
Although we and other studies indicated ZNF217 expression was increased in prostate cancer (PCa), the factors mediating its misregulated expression and their oncogenic activity remain largely unexplored. Recent evidence demonstrated that ferroportin (FPN) reduction lead to decreased iron export and increased intercellular iron that consequently aggravates the oncogenic effects of iron. In the present study, ZNF217 was identified as a transcriptional repressor that inhibits FPN expression. Increased of ZNF217 expression led to decreased FPN concentration, coupled with resultant intracellular iron retention, increased iron-related cellular activities and enhanced tumor cell growth. In contrast, decreased of ZNF217 expression restrained tumor cell growth by promoting FPN-driven iron egress. Mechanistic investigation manifested that ZNF217 facilitated the H3K27me3 levels of FPN promoter by interacting with EZH2. Besides, we also found that MAZ increased the transcription level of ZNF217, and subsequently inhibited the FPN expression and their iron–related activities. Strikingly, the expression of MAZ, EZH2 and ZNF217 were concurrently upregulated in PCa, leading to decreased expression of FPN, which induce disordered iron metabolism. Collectively, this study underscored that elevated expression of ZNF217 promotes prostate cancer growth by restraining FPN-conducted iron egress.
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