The long non-coding RNA ERIC is regulated by E2F and modulates the cellular response to DNA damage

Molecular Cancer

Research

Jasmine Jacob¹  Gideon Rechavi¹  Tal Nizri²  Tirza Doniger²  Orit Feldstein²  Doron Ginsberg² 

[1] Cancer Research Center, Chaim Sheba Medical Center, Tel Hashomer, Israel;Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, 52900, Ramat Gan, Israel;

关键词: E2F1;    Long non-coding RNA;    Apoptosis;   

DOI  :  10.1186/1476-4598-12-131

 received in 2013-06-30, accepted in 2013-10-01,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundThe human genome encodes thousands of unique long non-coding RNAs (lncRNAs), and these transcripts are emerging as critical regulators of gene expression and cell fate. However, the transcriptional regulation of their expression is not fully understood. The pivotal transcription factor E2F1 which can induce both proliferation and cell death, is a critical downstream target of the tumor suppressor, RB. The retinoblastoma pathway is often inactivated in human tumors resulting in deregulated E2F activity.ResultsHere, we report that lncRNA XLOC 006942, which we named ERIC, is regulated by E2F1 and, most probably, also E2F3. We show that expression levels of ERIC were elevated upon activation of exogenous E2F1, E2F3 or endogenous E2Fs. Moreover, knockdown of either E2F1 or E2F3 reduced ERIC levels and endogenous E2F1 binds ERIC’s promoter. Expression of ERIC was cell cycle regulated and peaked in G1 in an E2F1-dependent manner. Inhibition of ERIC expression increased E2F1-mediated apoptosis, suggesting that E2F1 and ERIC constitute a negative feedback loop that modulates E2F1 activity. Furthermore, ERIC levels were increased following DNA damage by the chemotherapeutic drug Etoposide, and inhibition of ERIC expression enhanced Etoposide -induced apoptosis.ConclusionsOur data identify ERIC as a novel lncRNA that is transcriptionally regulated by E2Fs, and restricts apoptosis induced by E2F1, as well as by DNA damage.

【 授权许可】

Unknown   
© Feldstein et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.