A novel miRNA inhibits metastasis of prostate cancer via decreasing CREBBP-mediated histone acetylation
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ORIGINAL ARTICLE – CANCER RESEARCH
A novel miRNA inhibits metastasis of prostate cancer via decreasing CREBBP‑mediated histone acetylation Fubo Wang1 · Wei Zhang1 · Zijian Song1 · Maoyu Wang1 · Hanxiao Wu1 · Yang Yang2 · Rui Chen1 Received: 13 June 2020 / Accepted: 5 November 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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. Keywords MicroRNAs · Prostate cancer · miR-N5 · Metastasis · CREBBP · Histone acetylation Abbreviations miRNA MicroRNA CREBBP CREB-binding protein H3K56ac Histone 3 lysine56 acetylation PCa Prostate cancer CRPC Castration-resistant prostate cancer cells 3′-UTR 3′-Untranslated Regions MSKCC Memorial Sloan Kettering Cancer Center CHIP Chromatin Immunoprecipitation TCGA The Cancer Genome Atlas Fubo Wang and Wei Zhang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03455-9) contains supplementary material, which is available to authorized users. * Yang Yang [email protected] * Rui Chen [email protected] 1
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
2
Introduction Prostate cancer is the most prevalent malignancy in male genitourinary system. Due to the enlarged population of aging, the incidence of prostate cancer was increased fast in China (Chen et al. 2016). Approximately three-quarters of aging males suffered from prostate cancer (Zuniga et al. 2019). Despite the development of hormone deprivation therapy and surgery, a part of patients with localized prostate cancer experienced bone metastasis or visceral metastasis (Quiroz-Munoz et al. 2019). Therefore, it is of great significance to identify the mechanisms of prostate cancer metastasis and illustrate potential targets for advanced prostate cancer. Mature microRNAs are non-coding RNAs with a length of 18–25 nucleotides. It has already k
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