一种新的 miRNA 通过降低 CREBBP 介导的组蛋白乙酰化来抑制前列腺癌的转移。
A novel miRNA inhibits metastasis of prostate cancer via decreasing CREBBP-mediated histone acetylation.
机构信息
Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.
Institute of Clinical Laboratory Medicine, Clinical School of Medical College, Jinling Hospital, Nanjing University, Nanjing, China.
出版信息
J Cancer Res Clin Oncol. 2021 Feb;147(2):469-480. doi: 10.1007/s00432-020-03455-9. Epub 2020 Nov 21.
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, β-catenin and CDH1.
CONCLUSION
This study may shed the light on miR-N5 which influences metastasis via histone acetylation.
背景
为了鉴定与前列腺癌转移相关的新型 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 程序重新分析新型 miRNA。通过 Transwell 实验和集落形成实验分析 miR-N5 的生物学功能。通过生物信息学分析分析 miR-N5 的靶基因。通过 The Cancer Genome Atlas (TCGA) 和 Memorial Sloan Kettering Cancer Center (MSKCC) 数据库对下游靶基因进行分析，并通过 CHIP 实验进行验证。
结果
我们鉴定了一种新型 miRNA-miR-N5，其在 PCa 细胞、PCa 组织和前列腺癌患者的血清中下调。miR-N5 的敲除增强了体外迁移和侵袭能力。miR-N5 特异性靶向 CREBBP 3'-UTR 并抑制 CREBBP 表达，从而介导 EGFR、β-catenin 和 CDH1 启动子处的 H3K56 乙酰化。
结论
本研究可能揭示了 miR-N5 通过组蛋白乙酰化影响转移的机制。
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