دورية أكاديمية
Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer.
العنوان: | Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer. |
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المؤلفون: | Cheng CL; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Tsang FH; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Wei L; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Chen M; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Chin DW; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Shen J; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Law CT; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Lee D; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Wong CC; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Ng IO; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong., Wong CM; State Key Laboratory of Liver Research, The University of Hong Kong, Pok Fu Lam, Hong Kong. jackwong@pathology.hku.hk.; Department of Pathology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong. jackwong@pathology.hku.hk. |
المصدر: | Communications biology [Commun Biol] 2021 Jul 20; Vol. 4 (1), pp. 888. Date of Electronic Publication: 2021 Jul 20. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group UK Country of Publication: England NLM ID: 101719179 Publication Model: Electronic Cited Medium: Internet ISSN: 2399-3642 (Electronic) Linking ISSN: 23993642 NLM ISO Abbreviation: Commun Biol Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London, United Kingdom : Nature Publishing Group UK, [2018]- |
مواضيع طبية MeSH: | Transcriptional Activation*, Adaptor Proteins, Signal Transducing/*genetics , Carcinoma, Hepatocellular/*drug therapy , DNA-Binding Proteins/*genetics , Liver Neoplasms/*drug therapy, Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Carcinoma, Hepatocellular/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Liver Neoplasms/genetics ; Male ; Mice ; Mice, Inbred BALB C |
مستخلص: | Epigenetic deregulation plays an essential role in hepatocellular carcinoma (HCC) progression. Bromodomains are epigenetic "readers" of histone acetylation. Recently, bromodomain inhibitors have exhibited promising therapeutic potential for cancer treatment. Using transcriptome sequencing, we identified BRPF1 (bromodomain and PHD finger containing 1) as the most significantly upregulated gene among the 43 bromodomain-containing genes in human HCC. BRPF1 upregulation was significantly associated with poor patient survival. Gene ablation or pharmacological inactivation of BRPF1 significantly attenuated HCC cell growth in vitro and in vivo. BRPF1 was involved in cell cycle progression, senescence and cancer stemness. Transcriptome sequencing revealed that BRPF1 is a master regulator controlling the expression of multiple key oncogenes, including E2F2 and EZH2. We demonstrated that BRPF1 activated E2F2 and EZH2 expression by facilitating promoter H3K14 acetylation through MOZ/MORF complex. In conclusion, BRPF1 is frequently upregulated in human HCCs. Targeting BRPF1 may be an approach for HCC treatment. (© 2021. The Author(s).) |
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المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (BRPF1 protein, human) 0 (DNA-Binding Proteins) |
تواريخ الأحداث: | Date Created: 20210721 Date Completed: 20211111 Latest Revision: 20211111 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8292510 |
DOI: | 10.1038/s42003-021-02405-6 |
PMID: | 34285329 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2399-3642 |
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DOI: | 10.1038/s42003-021-02405-6 |