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A novel miRNA inhibits metastasis of prostate cancer via decreasing CREBBP-mediated histone acetylation

机译:一种新的miRNA通过降低Crebbp介导的组蛋白乙酰化抑制前列腺癌转移

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Background To identify novel miRNAs implicated in prostate cancer metastasis. Methods Sixty-five prostate cancer tissues and paired pan-cancer tissues were sequenced. Novel miRNAs were re-analyzed by MIREAP program. Biological functions of miR-N5 were transwell experiment and colony formation. Target genes of miR-N5 were analyzed by bioinformatic analysis. Downstream of target gene was analyzed by The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering Cancer Center (MSKCC) databases and confirmed by CHIP experiment. Results We identified a novel miRNA-miR-N5, which was downregulated in PCa cells, PCa tissue, and in the serum of patients with PCa. Knockout of miR-N5 enhanced migration and invasiveness in vitro. miR-N5 specified targeted CREBBP 3 '-UTR and inhibited CREBBP expression, which mediated H3K56 acetylation at the promoter of EGFR, beta-catenin and CDH1. Conclusion This study may shed the light on miR-N5 which influences metastasis via histone acetylation.
机译:背景:鉴定与前列腺癌转移相关的新miRNA。方法对65例前列腺癌组织和配对的泛癌组织进行测序。通过MIREAP程序重新分析新的miRNA。miR-N5的生物学功能包括跨孔实验和菌落形成。通过生物信息学分析miR-N5的靶基因。通过癌症基因组图谱(TCGA)和纪念斯隆-凯特林癌症中心(MSKCC)数据库对目标基因下游进行分析,并通过芯片实验进行确认。结果我们发现了一种新的miRNA-miR-N5,其在PCa细胞、PCa组织和PCa患者血清中表达下调。在体外,敲除miR-N5可增强迁移和侵袭性。miR-N5指定靶向CREBBP 3'-UTR并抑制CREBBP表达,其在EGFR、β-连环蛋白和CDH1的启动子处介导H3K56乙酰化。结论本研究可能为miR-N5通过组蛋白乙酰化影响肿瘤转移提供了线索。

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