Scientific publications

Long Noncoding RNA EGOT Responds to Stress Signals to Regulate Cell Inflammation and Growth

Apr 15, 2021 | Magazine: Journal of Immunology

Marina Barriocanal  1   2 , Celia Prior  1   2 , Beatriz Suarez  1 , Juan Pablo Unfried  1 , Nerea Razquin  1 , Sandra Hervás-Stubbs  3   4   5 , Bruno Sangro  2   4   5 , Victor Segura  4   6 , Puri Fortes  7   4   5


Abstract

The cell has several mechanisms to sense and neutralize stress. Stress-related stimuli activate pathways that counteract danger, support cell survival, and activate the inflammatory response.

We use human cells to show that these processes are modulated by EGOT, a long noncoding RNA highly induced by viral infection, whose inhibition results in increased levels of antiviral IFN-stimulated genes (ISGs) and decreased viral replication.

We now show that EGOT is induced in response to cell stress, viral replication, or the presence of pathogen-associated molecular patterns via the PI3K/AKT, MAPKs, and NF-κB pathways, which lead to cell survival and inflammation. Transcriptome analysis and validation experiments show that EGOT modulates PI3K/AKT and NF-κB responses.

On the one hand, EGOT inhibition decreases expression of PI3K/AKT-induced cellular receptors and cell proliferation. In fact, EGOT levels are increased in several tumors. On the other hand, EGOT inhibition results in decreased levels of key NF-κB target genes, including those required for inflammation and ISGs in those cells that build an antiviral response. Mechanistically, EGOT depletion decreases the levels of the key coactivator TBLR1, essential for transcription by NF-κB.

In summary, EGOT is induced in response to stress and may function as a switch that represses ISG transcription until a proper antiviral or stress response is initiated. EGOT then helps PI3K/AKT, MAPKs, and NF-κB pathways to activate the antiviral response, cell inflammation, and growth. We believe that modulation of EGOT levels could be used as a therapy for the treatment of certain viral infections, immune diseases, and cancer.

CITATION  J Immunol. 2021 Apr 15;206(8):1932-1942.  doi: 10.4049/jimmunol.1900776.  Epub 2021 Mar 31.

Our authors

Celia Prior Darbonnens
Juan Pablo Unfried Huertas
Nerea Razquin Erro
Dr. Sandra Hervás Stubbs
Researcher | Principal Investigator Adoptive Cell Therapy Research Group