Oncotarget

Research Papers:

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 and Doron Ginsberg _

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Oncotarget. 2017; 8:23775-23786. https://doi.org/10.18632/oncotarget.15864

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Abstract

Lital Gasri-Plotnitsky1, Aviv Ovadia1, Katerina Shamalov1, Tali Nizri-Megnaji1, Shimrit Meir1, Irit Zurer1, Cyrille J. Cohen1, Doron Ginsberg1

1The Mina and Everard Goodman Faculty of Life Science, Bar Ilan University, Ramat Gan 52900, Israel

Correspondence to:

Doron Ginsberg, email: doron.ginsberg@biu.ac.il

Keywords: lncRNA, cell cycle, cell proliferation, E2F

Received: June 29, 2016     Accepted: February 10, 2017     Published: March 03, 2017

ABSTRACT

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.


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