A novel lncRNA, GASL1, inhibits cell proliferation and restricts E2F1 activity

Lital Gasri-Plotnitsky, Aviv Ovadia, Katerina Shamalov, Tali Nizri-Megnaji, Shimrit Meir, Irit Zurer, Cyrille J. Cohen, Doron Ginsberg

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


The human genome encodes thousands of unique long non-coding RNAs (lncRNAs), many of which are emerging as critical regulators of cell fate. However, their functions as well as their transcriptional regulation are only partially understood. The E2F1 transcription factor induces both proliferation and apoptosis, and is a critical downstream target of the tumor suppressor, RB. Here, we provide evidence that a novel lncRNA named GASL1 is transcriptionally regulated by E2F1; GASL1 levels are elevated upon activation of exogenous E2F1 or endogenous E2Fs. Inhibition of GASL1 expression induced cell cycle progression, and in particular, G1 exit. Moreover, GASL1 silencing enhanced cell proliferation, while, conversely, its ectopic expression inhibited proliferation. Knockdown of GASL1 also enhanced E2F1-induced apoptosis, suggesting the existence of an E2F/GASL1 negative feedback loop. In agreement with this notion, silencing of GASL1 led to increased levels of phosphorylated pRB and loss of Rb impaired the effect of GASL1 silencing on G1 exit. Importantly, xenograft experiments demonstrated that GASL1 deletion enhances tumor growth. Moreover, low levels of GASL1 are associated with decreased survival of liver cancer patients. Taken together, our data identify GASL1 as a novel lncRNA regulator of cell cycle progression and cell proliferation with a potential role in cancer.

Original languageEnglish
Pages (from-to)23775-23786
Number of pages12
Issue number14
StatePublished - 4 Apr 2017

Bibliographical note

Funding Information:
We thank Yoav Elkis for assistance with in vivo experiments, Or Bida-Dabush and Shlomit Brodie for reagents, and Ilana Lebenthal-Loinger for computational analysis. We thank all members of the Ginsberg group for helpful discussions and critical reading of the manuscript. This work was supported by grants from the Israel Cancer Research Association (ICRF), the Israel Cancer Association (ICA) and the Cooperation Program in Cancer Research DKFZ-MOST to D.G.


  • Cell cycle
  • Cell proliferation
  • E2F
  • LncRNA


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