Document detail
ID

oai:pubmedcentral.nih.gov:1000...

Topic
Article
Author
Carrillo, David Reggiardo, Roman E. Lim, John Mantalas, Gary Peddu, Vikas Kim, Daniel H.
Langue
en
Editor

Cold Spring Harbor Laboratory

Category

biorxiv

Year

2023

listing date

3/15/2023

Keywords
rna cancer lung rnas kras te
Metrics

Abstract

Mutant KRAS regulates transposable element (TE) RNA and interferon-stimulated gene (ISG) expression, but it remains unclear whether diverse mutations in KRAS affect different TE RNAs throughout the genome.

We analyzed the transcriptomes of 3D human lung cancer spheroids that harbor KRAS(G12C) mutations to determine the landscape of TE RNAs regulated by mutant KRAS(G12C).

We found that KRAS(G12C) signaling is required for the expression of LINE- and LTR-derived TE RNAs that are distinct from TE RNAs previously shown to be regulated by mutant KRAS(G12D) or KRAS(G12V).

Moreover, KRAS(G12C) inhibition specifically upregulates SINE-derived TE RNAs from the youngest Alu subfamily AluY.

Our results reveal that TE RNA dysregulation in KRAS-driven lung cancer cells is mutation-dependent, while also highlighting a subset of young, Alu-derived TE RNAs that are coordinately activated with innate immunity genes upon KRAS(G12C) inhibition.

Carrillo, David,Reggiardo, Roman E.,Lim, John,Mantalas, Gary,Peddu, Vikas,Kim, Daniel H., 2023, Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids , Cold Spring Harbor Laboratory

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