RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer.
RNF20 Is Critical for Snail-Mediated E-Cadherin Repression in Human Breast Cancer.
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RNF20 对于人类乳腺癌中蜗牛介导的 E-钙粘蛋白抑制至关重要
DOI：
10.3389/fonc.2020.613470
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发表时间：
2020
影响因子：
4.7
通讯作者：
Dong C
中科院分区：
文献类型：
--
作者：
Wang D;Wang Y;Wu X;Kong X;Li J;Dong C
上皮-间质转化（EMT）的标志性蛋白E-钙粘蛋白常因Snail介导的表观遗传修饰而受到抑制，但其确切机制尚不清楚。迫切需要了解肿瘤侵袭性的决定因素，并确定乳腺癌的潜在治疗靶点。实验设计我们通过免疫共沉淀研究了RNF 20与Snail和G9 a的结合。我们采用实时定量PCR、ChIP、transwell法、克隆形成法和mammosphere法来分析与人乳腺癌中E-cadherin抑制相关的分子事件。我们使用包含105个乳腺肿瘤样本的蛋白基因组数据集，通过Kaplan-Meier分析确定RNF 20的临床相关性。结果在本研究中，我们确定Snail与RNF 20和G9 a相互作用，RNF 20是一种E3泛素蛋白连接酶，负责H2 BK 120的单泛素化，G9 a是H3 K9 me 2的甲基转移酶。RNF 20的表达导致人乳腺癌细胞中E-钙粘蛋白表达的抑制。从机制上讲，我们发现RNF 20和H3 K9 m2富集在E-钙粘蛋白的启动子上，Snail的敲除减少了RNF 20的富集，显示出Snail依赖性方式。RNF 20表达增强乳腺癌细胞的迁移、侵袭、肿瘤球和集落形成。临床上，RNF 20高表达的患者总生存期较短。结论RNF 20表达通过Snail介导的E-cadherin表达的表观遗传抑制参与EMT的诱导和乳腺癌的进展，提示RNF 20在乳腺癌中的重要性。
Background E-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often repressed due to Snail-mediated epigenetic modification; however, the exact mechanism remains unclear. There is an urgent need to understand the determinants of tumor aggressiveness and identify potential therapeutic targets in breast cancer. Experimental design We studied the association of RNF20 with Snail and G9a by co-immunoprecipitation. We employed quantitative real-time PCR, ChIP, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the repression of E-cadherin in human breast cancer. We used a proteogenomic dataset that contains 105 breast tumor samples to determine the clinical relevance of RNF20 by Kaplan-Meier analyses. Results In this study, we identified that Snail interacted with RNF20, an E3 ubiquitin-protein ligase responsible for monoubiquitination of H2BK120, and G9a, a methyltransferase for H3K9me2. RNF20 expression led to the inhibition of E-cadherin expression in the human breast cancer cells. Mechanically, we showed that RNF20 and H3K9m2 were enriched on the promoter of E-cadherin and knockdown of Snail reduced the enrichment of RNF20, showing a Snail-dependent manner. RNF20 expression enhanced breast cancer cell migration, invasion, tumorsphere and colony formation. Clinically, patients with high RNF20 expression had shorter overall survival. Conclusion RNF20 expression contributes to EMT induction and breast cancer progression through Snail-mediated epigenetic suppression of E-cadherin expression, suggesting the importance of RNF20 in breast cancer.
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DOI：
10.1186/bcr2106
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Grimshaw MJ;Cooper L;Papazisis K;Coleman JA;Bohnenkamp HR;Chiapero-Stanke L;Taylor-Papadimitriou J;Burchell JM
通讯作者：
Burchell JM
影响因子：
45.3
作者：
Liu, Suling;Wicha, Max S.
通讯作者：
Wicha, Max S.
影响因子：
11.2
作者：
Chernikova SB;Razorenova OV;Higgins JP;Sishc BJ;Nicolau M;Dorth JA;Chernikova DA;Kwok S;Brooks JD;Bailey SM;Game JC;Brown JM
通讯作者：
Brown JM
影响因子：
51.1
作者：
Badve, Sunil;Nakshatri, Harikrishna
通讯作者：
Nakshatri, Harikrishna
影响因子：
4.8
作者：
Krogan, NJ;Dover, J;Shilatifard, A
通讯作者：
Shilatifard, A