UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation
UHRF1 promotes proliferation of gastric cancer via mediating tumor suppressor gene hypermethylation
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UHRF1通过介导抑癌基因高甲基化促进胃癌增殖。
DOI：
10.1080/15384047.2015.1056411
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发表时间：
2015-08-01
影响因子：
3.6
通讯作者：
Liang, Jie
中科院分区：
文献类型：
--
作者：
Zhou, Lin;Shang, Yulong;Liang, Jie
表观遗传变化在癌症发展中发挥着重要作用。 UHRF1 是一种表观遗传调节因子，已被证明在多种癌症中过度表达并协调肿瘤抑制基因 (TSG) 沉默。在之前的研究中，我们发现UHRF1促进胃癌（GC）的侵袭和转移。然而，UHRF1在GC癌变中的作用和潜在机制仍然很大程度上未知。在本研究中，我们研究了UHRF1在GC增殖中的表达和功能，并探讨了其下游调控机制。结果表明，UHRF1 过表达是 GC 预后的独立且重要的预测因子。 UHRF1 的下调在体外和体内抑制 GC 增殖和生长，而 UHRF1 的上调则表现出相反的效果。此外，UHRF1 的下调通过启动子去甲基化重新激活了 7 个 TSG，包括 CDX2、CDKN2A、RUNX3、FOXO4、PPARG、BRCA1 和 PML。这些结果提供了对 GC 增殖过程的深入了解，并表明靶向 UHRF1 代表了一种阻止 GC 发展的新治疗方法。
Epigenetic changes play significant roles in cancer development. UHRF1, an epigenetic regulator, has been shown to be overexpressed and to coordinate tumor suppressor gene (TSG) silencing in several cancers. In a previous study, we found that UHRF1 promoted gastric cancer (GC) invasion and metastasis. However, the role and underlying mechanism of UHRF1 in GC carcinogenesis remain largely unknown. In the present study, we investigated UHRF1 expression and function in GC proliferation and explored its downstream regulatory mechanism. The results demonstrated that UHRF1 overexpression was an independent and significant predictor of GC prognosis. Downregulation of UHRF1 suppressed GC proliferation and growth in vitro and in vivo, and UHRF1 upregulation showed opposite effects. Furthermore, downregulation of UHRF1 reactivated 7 TSGs, including CDX2, CDKN2A, RUNX3, FOXO4, PPARG, BRCA1 and PML, via promoter demethylation. These results provide insight into the GC proliferation process, and suggest that targeting UHRF1 represents a new therapeutic approach to block GC development.