CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription.
CAPG enhances breast cancer metastasis by competing with PRMT5 to modulate STC-1 transcription.
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CAPG 通过与 PRMT5 竞争调节 STC-1 转录来增强乳腺癌转移
作者：
Huang S;Chi Y;Qin Y;Wang Z;Xiu B;Su Y;Guo R;Guo L;Sun H;Zeng C;Zhou S;Hu X;Liu S;Shao Z;Wu Z;Jin W;Wu J
巨噬细胞帽蛋白（CAPG）已被证明可以促进癌细胞转移，尽管其机制仍然知之甚少。方法：应用乳腺癌组织芯片检测CAPG在乳腺癌患者预后中的作用。采用异种移植小鼠模型验证CAPG在体内的促转移作用。采用基因表达谱芯片、染色质免疫沉淀和荧光素酶报告试验等方法寻找CAPG的靶基因。采用蛋白质免疫沉淀、MS/MS分析、组织芯片和组蛋白甲基转移酶分析等方法探讨CAPG调控斯钙素1（stanniocalcin 1，STC-1）转录的机制。结果如下：我们证明了CAPG通过促进促转移基因STC-1的转录来增强BC转移的新机制，有助于增加BC的转移。在机制上，CAPG与转录抑制因子精氨酸甲基转移酶5（PRMT 5）竞争结合STC-1启动子，导致组蛋白H4 R3甲基化降低和STC-1转录增强。我们的研究还表明，CAPG和PRMT 5是BC患者生存的独立预后因素。高CAPG水平与生存率差相关，而PRMT 5高表达有利于BC患者的预后。结论：我们的研究结果确定了一个新的作用，CAPG在促进BC转移的表观遗传学增强STC-1的转录。
Macrophage-capping protein (CAPG) has been shown to promote cancer cell metastasis, although the mechanism remains poorly understood. Methods: Breast cancer (BC) tissue microarray was used to test the role of CAPG in the prognosis of BC patients. Xenograft mice model was used to validate the metastasis promotion role of CAPG in vivo. Gene expression array, chromatin immunoprecipitation and luciferase report assay were performed to search for the target genes of CAPG. Protein immunoprecipitation, MS/MS analysis, tissue microarray and histone methyltransferase assay were used to explore the mechanism of CAPG regulating stanniocalcin 1 (STC-1) transcription. Results: We demonstrate a novel mechanism by which CAPG enhances BC metastasis via promoting the transcription of the pro-metastatic gene STC-1, contributing to increased metastasis in BC. Mechanistically, CAPG competes with the transcriptional repressor arginine methyltransferase 5 (PRMT5) for binding to the STC-1 promoter, leading to reduced histone H4R3 methylation and enhanced STC-1 transcription. Our study also indicates that both CAPG and PRMT5 are independent prognostic factors for BC patient survival. High CAPG level is associated with poor survival, while high PRMT5 expression favors a better prognosis in BC patients. Conclusion: Our findings identify a novel role of CAPG in the promotion of BC metastasis by epigenetically enhancing STC-1 transcription.
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影响因子：
3.8
作者：
Chi Y;Huang S;Wang L;Zhou R;Wang L;Xiao X;Li D;Cai Y;Zhou X;Wu J
通讯作者：
Wu J
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影响因子：
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Friesen, WJ;Wyce, A;Dreyfuss, G
通讯作者：
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作者：
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