Li Shuyan, Sun Ao, Liang Xiuming, Ma Lin, Shen Li, Li Tongyu, Zheng Lixin, Shang Wenjing, Zhao Wei, Jia Jihui
Department of Microbiology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University Jinan 250012, Shandong, PR China.
Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University Jinan 250012, Shandong, PR China.
Am J Cancer Res. 2017 Mar 1;7(3):448-461. eCollection 2017.
Histone demethylase plant homeodomain (PHD) finger protein 8 (PHF8) has been implicated in tumor development and malignant progression in various types of cancers. However, its potential roles in gastric cancer (GC) have not been explored. In this report, we show that PHF8 expression is upregulated in GC tissues, and the enhanced PHF8 level indicates a poor prognosis of GC patients. PHF8 knockdown reduces proliferation and metastasis of GC cells, while PHF8 overexpression has the opposite effects. Mechanistically, PHF8 interacts with β-catenin, and binds to the promoter region of vimentin, leading to the promotion of vimentin transcription. In addition, we show that , the single most important risk factor for GC, markedly induce PHF8 expression. Our results suggest that -induced PHF8-β-catenin-vimentin axis activation is a novel mechanism for GC malignant progression. Thus, we identify PHF8 as an oncogenic factor of GC, and suggest PHF8 might be a potential molecular target for therapeutic approaches for GC.
组蛋白去甲基化酶植物同源结构域（PHD）指蛋白8（PHF8）与多种癌症的肿瘤发生和恶性进展有关。然而，其在胃癌（GC）中的潜在作用尚未得到探索。在本报告中，我们发现PHF8在GC组织中表达上调，且PHF8水平升高表明GC患者预后不良。敲低PHF8可降低GC细胞的增殖和转移，而PHF8过表达则有相反的作用。机制上，PHF8与β-连环蛋白相互作用，并与波形蛋白的启动子区域结合，从而促进波形蛋白的转录。此外，我们发现，作为GC最重要的单一危险因素，显著诱导PHF8表达。我们的结果表明，诱导的PHF8-β-连环蛋白-波形蛋白轴激活是GC恶性进展的一种新机制。因此，我们将PHF8鉴定为GC的致癌因子，并表明PHF8可能是GC治疗方法的潜在分子靶点。
