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

Area of Science:

• Cellular stress response
• Innate immunity
• Noncoding RNA biology

Background:

• Cells possess mechanisms to detect and respond to stress, involving pathways that promote survival and inflammation.
• Long noncoding RNAs (lncRNAs) play regulatory roles in cellular processes, including immunity.
• EGOT is a lncRNA induced by viral infections, impacting antiviral gene expression.

Purpose of the Study:

• To investigate the role of EGOT in cellular stress responses and its modulation of key signaling pathways.
• To determine the impact of EGOT inhibition on antiviral gene expression, viral replication, and cell proliferation.
• To explore the therapeutic potential of targeting EGOT in viral infections, immune disorders, and cancer.

Main Methods:

• Human cell models were used to study EGOT induction and function.
• Transcriptome analysis (RNA sequencing) was performed to identify EGOT-regulated genes.
• Validation experiments confirmed the effects of EGOT inhibition on specific pathways and gene expression.

Main Results:

• EGOT is induced by cell stress, viral replication, and pathogen-associated molecular patterns via PI3K/AKT, MAPKs, and NF-κB pathways.
• EGOT inhibition increases antiviral IFN-stimulated genes (ISGs) and decreases viral replication.
• EGOT modulates PI3K/AKT and NF-κB signaling, affecting cell proliferation and inflammatory gene expression. EGOT depletion reduces TBLR1 coactivator levels, impacting NF-κB transcription.

Conclusions:

• EGOT acts as a switch, repressing ISG transcription until a stress or antiviral response is initiated.
• EGOT facilitates PI3K/AKT, MAPK, and NF-κB pathway activation for antiviral responses, inflammation, and cell growth.
• Modulating EGOT levels presents a potential therapeutic strategy for viral infections, immune diseases, and cancer.