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本文引用的文献

1
Epigenetic programming and reprogramming during development.发育过程中的表观遗传编程和重编程。
Nat Struct Mol Biol. 2013 Mar;20(3):282-9. doi: 10.1038/nsmb.2489. Epub 2013 Mar 5.
2
miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4.miR-7 通过调节 KLF4 抑制乳腺癌干细胞样细胞的脑转移。
Cancer Res. 2013 Feb 15;73(4):1434-44. doi: 10.1158/0008-5472.CAN-12-2037. Epub 2013 Feb 5.
3
Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer.抑癌基因视网膜母细胞瘤的表观遗传沉默调控肿瘤中髓系细胞的病理性分化。
Nat Immunol. 2013 Mar;14(3):211-20. doi: 10.1038/ni.2526. Epub 2013 Jan 27.
4
microRNA-7 is a novel inhibitor of YY1 contributing to colorectal tumorigenesis.microRNA-7 是一种新型的 YY1 抑制剂，有助于结直肠肿瘤的发生。
Oncogene. 2013 Oct 17;32(42):5078-88. doi: 10.1038/onc.2012.526. Epub 2012 Dec 3.
5
Aberrant overexpression of miR-421 downregulates ATM and leads to a pronounced DSB repair defect and clinical hypersensitivity in SKX squamous cell carcinoma.异常过表达的 miR-421 下调 ATM 表达，导致 SKX 鳞状细胞癌中明显的 DSB 修复缺陷和临床敏感性增加。
Radiother Oncol. 2013 Jan;106(1):147-54. doi: 10.1016/j.radonc.2012.10.020. Epub 2012 Nov 28.
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Characterization of the EZH2-MMSET histone methyltransferase regulatory axis in cancer.鉴定癌症中 EZH2-MMSET 组蛋白甲基转移酶调控轴。
Mol Cell. 2013 Jan 10;49(1):80-93. doi: 10.1016/j.molcel.2012.10.008. Epub 2012 Nov 15.
7
High-throughput microRNA (miRNAs) arrays unravel the prognostic role of MiR-211 in pancreatic cancer.高通量 microRNA（miRNAs）芯片揭示了 MiR-211 在胰腺癌中的预后作用。
PLoS One. 2012;7(11):e49145. doi: 10.1371/journal.pone.0049145. Epub 2012 Nov 14.
8
Regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by miR-7.miR-7 调控头颈部癌细胞中表皮生长因子受体信号通路和厄洛替尼敏感性
PLoS One. 2012;7(10):e47067. doi: 10.1371/journal.pone.0047067. Epub 2012 Oct 24.
9
RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1.RING 指核因子 RNF168 对于乳腺癌易感性因子 BRCA1 缺失引起的同源重组缺陷很重要。
J Biol Chem. 2012 Nov 23;287(48):40618-28. doi: 10.1074/jbc.M112.410951. Epub 2012 Oct 10.
10
MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression.MicroRNA-7 通过靶向 FAK 表达抑制乳腺癌细胞的上皮间质转化和转移。
PLoS One. 2012;7(8):e41523. doi: 10.1371/journal.pone.0041523. Epub 2012 Aug 2.

microRNA-7 通过靶向组蛋白甲基转移酶 SET8 抑制乳腺癌细胞的侵袭能力并使细胞对 DNA 损伤敏感。

microRNA-7 suppresses the invasive potential of breast cancer cells and sensitizes cells to DNA damages by targeting histone methyltransferase SET8.

机构信息

Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing 100191, China.

出版信息

J Biol Chem. 2013 Jul 5;288(27):19633-42. doi: 10.1074/jbc.M113.475657. Epub 2013 May 17.

DOI:10.1074/jbc.M113.475657
PMID:23720754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3707664/
Abstract

SET8 (SET domain containing 8) is a histone H4 lysine 20 (H4K20)-specific monomethyltransferase in higher eukaryotes that exerts diverse functions in transcription regulation, DNA repair, tumor metastasis, and genome integrity. The activity of SET8 is tightly controlled during cell cycle through post-translational modifications, including ubiquitination, phosphorylation, and sumoylation. However, how the expression of SET8 is regulated is not fully understood. Here, we report that microRNA-7 is a negative regulator of SET8. We demonstrated that microRNA-7 inhibits H4K20 monomethylation and suppresses epithelial-mesenchymal transition and the invasive potential of breast cancer cells. We showed that microRNA-7 promotes spontaneous DNA damages and sensitizes cells to induced DNA damages. Our experiments provide a molecular mechanism for the regulation of SET8 and extend the biological function of microRNA-7 to DNA damage response, supporting the pursuit of microRNA-7 as a potential target for breast cancer intervention.

摘要

SET8（SET 结构域包含 8 个）是高等真核生物中组蛋白 H4 赖氨酸 20（H4K20）特异性单甲基转移酶，在转录调控、DNA 修复、肿瘤转移和基因组完整性方面发挥着多种功能。SET8 的活性通过翻译后修饰（包括泛素化、磷酸化和 sumoylation）在细胞周期中受到严格控制。然而，SET8 的表达是如何被调控的还不完全清楚。在这里，我们报告 microRNA-7 是 SET8 的负调控因子。我们证明了 microRNA-7 抑制 H4K20 单甲基化，并抑制乳腺癌细胞的上皮-间充质转化和侵袭潜能。我们表明 microRNA-7 促进自发的 DNA 损伤，并使细胞对诱导的 DNA 损伤敏感。我们的实验为 SET8 的调控提供了一个分子机制，并将 microRNA-7 的生物学功能扩展到 DNA 损伤反应，支持将 microRNA-7 作为乳腺癌干预的潜在靶点进行研究。