MiR-502/SET8 regulatory circuit in pathobiology of breast cancer
MiR-502/SET8 regulatory circuit in pathobiology of breast cancer
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MiR-502/SET8 调控电路在乳腺癌病理学中的应用
DOI：
10.1016/j.canlet.2016.04.008
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发表时间：
2016-07-01
期刊：
影响因子：
9.7
通讯作者：
Chen, Kexin
中科院分区：
文献类型：
--
作者：
Liu, Ben;Zhang, Xining;Chen, Kexin
我们之前的研究和广泛的流行病学研究重复性地证明，miR-502可能靶向H4 K20甲基转移酶SETS在广泛的癌症中的表达。然而，miR-502对SETS的直接靶向作用尚未得到明确证实。miR-502/SET 8调节回路的临床意义也不清楚。在这里，我们在279个乳腺癌样本的队列中进行了基于细胞的实验和临床研究。我们提供的证据表明SET 8是miR-502的直接靶点。用miR-502或下调SET 8处理抑制细胞增殖和细胞周期，并减少细胞迁移、侵袭和EMT。临床分析显示miR-502在肿瘤组织中的表达低于癌旁组织，且与SET 8的表达呈显著负相关。此外，SET 8的高表达与乳腺癌的不良总生存期（OS）和无病生存期（DFS）显著相关。miR-502与SET 8 mRNA的低表达比率也与OS差显著相关。因此，miR-502/SET 8调节回路成为癌症病理生物学的关键调节器和可能的治疗干预的焦点。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Our previous research and extensive epidemiological studies reproducibly demonstrated that miR-502 potentially targeted the expression of H4K20 methyltransferase SETS in a wide spectrum of cancer. Yet, the direct targeting of SETS by miR-502 has not been definitively proven. The clinical significance of the miR-502/SET8 regulatory circuit is also not clear. Here, we conducted cell-based experiments and clinical studies in a cohort of 279 breast cancer samples. We provide evidence that SET8 is a direct target of miR-502. Treatment with miR-502 or downregulation of SET8 suppressed cell proliferation and cell cycle, and reduced cell migration, invasion and EMT. Clinical analyses showed the miR-502 expression was lower in tumor tissues than in adjacent non-tumor tissues and had a significant inverse correlation with that of SET8. Furthermore, high expression of SET8 was significantly associated with poor overall survival (OS) and disease free survival (DFS) of breast cancer. The low expression ratio of miR-502 to SET8 mRNA was also significantly associated with poor OS. Thus, the miR-502/SET8 regulatory circuit emerges as a key regulator of the pathobiology of cancer and a focal point for possible therapeutic intervention. (C) 2016 Elsevier Ireland Ltd. All rights reserved.