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有附件Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis

biocq 添加于 2012-3-25 14:17 | 2066 次阅读 | 0 个评论

  •  作 者

    Gupta RA, Shah N, Wang KC, Kim J, Horlings HM, Wong DJ, Tsai M-C, Hung T, Argani P, Rinn JL, Wang Y, Brzoska P, Kong B, Li R, West RB, van de Vijver MJ, Sukumar S, Chang HY

  •  摘 要

    Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.

  •  详细资料

    • 关键词: Animals; Breast Neoplasms/genetics/pathology; Cell Line, Tumor; Cell Proliferation; Chromatin/*genetics; Chromatin Assembly and Disassembly/*genetics; Disease Progression; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Genes, Homeobox/genetics; Genome, Human/genetics; Histones/metabolism; Humans; Methylation; Mice; Mice, Nude; Mice, SCID; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis/*genetics; Neoplasm Transplantation; Prognosis; RNA Interference; RNA, Untranslat ...
    • 文献种类: Journal Article
    • 期刊名称: Nature
    • 期刊缩写: Nature
    • 期卷页: 2010年  第464卷 第7291期 1071-1076页
    • 地址: Howard Hughes Medical Institute and Program in Epithelial Biology, California 94305, USA
    • ISBN: 0028-0836

  • 学科领域 生物医药 » 生物学

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  •  附 件

    PDF附件Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis 

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