Wan, Guohui; Hu, Xiaoxiao; Liu, Yunhua; Han, Cecil; Sood, Anil K; Calin, George A; Zhang, Xinna; Lu, Xiongbin
A novel non-coding RNA lncRNA-JADE connects DNA damage signalling to histone H4 acetylation
Teil von
  • The EMBO journal, 2013-10-30, Vol.32 (21), p.2833-2847
Ort / Verlag
Chichester, UK: John Wiley & Sons, Ltd
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HighWire Press (Free Journals)
A prompt and efficient DNA damage response (DDR) eliminates the detrimental effects of DNA lesions in eukaryotic cells. Basic and preclinical studies suggest that the DDR is one of the primary anti‐cancer barriers during tumorigenesis. The DDR involves a complex network of processes that detect and repair DNA damage, in which long non‐coding RNAs (lncRNAs), a new class of regulatory RNAs, may play an important role. In the current study, we identified a novel lncRNA, lncRNA‐JADE, that is induced after DNA damage in an ataxia‐telangiectasia mutated (ATM)‐dependent manner. LncRNA‐JADE transcriptionally activates Jade1, a key component in the HBO1 (human acetylase binding to ORC1) histone acetylation complex. Consequently, lncRNA‐JADE induces histone H4 acetylation in the DDR. Markedly higher levels of lncRNA‐JADE were observed in human breast tumours in comparison with normal breast tissues. Knockdown of lncRNA‐JADE significantly inhibited breast tumour growth in vivo. On the basis of these results, we propose that lncRNA‐JADE is a key functional link that connects the DDR to histone H4 acetylation, and that dysregulation of lncRNA‐JADE may contribute to breast tumorigenesis. ATM activation upon DNA damage induces the long non‐coding RNA lncRNA‐JADE, which associates with BRCA1 to stimulate expression of JADE1 and hence histone H4 acetylation. LncRNA‐JADE is highly expressed in breast cancer and required for tumour growth in vivo.

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