Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids

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) mutati...

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Autores principales: Carrillo, David, Reggiardo, Roman E., Lim, John, Mantalas, Gary, Peddu, Vikas, Kim, Daniel H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002638/
https://www.ncbi.nlm.nih.gov/pubmed/36909578
http://dx.doi.org/10.1101/2023.02.27.530369
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author Carrillo, David
Reggiardo, Roman E.
Lim, John
Mantalas, Gary
Peddu, Vikas
Kim, Daniel H.
author_facet Carrillo, David
Reggiardo, Roman E.
Lim, John
Mantalas, Gary
Peddu, Vikas
Kim, Daniel H.
author_sort Carrillo, David
collection PubMed
description 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.
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spelling pubmed-100026382023-03-11 Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids Carrillo, David Reggiardo, Roman E. Lim, John Mantalas, Gary Peddu, Vikas Kim, Daniel H. bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-02-28 /pmc/articles/PMC10002638/ /pubmed/36909578 http://dx.doi.org/10.1101/2023.02.27.530369 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Carrillo, David
Reggiardo, Roman E.
Lim, John
Mantalas, Gary
Peddu, Vikas
Kim, Daniel H.
Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids
title Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids
title_full Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids
title_fullStr Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids
title_full_unstemmed Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids
title_short Transposable element RNA dysregulation in mutant KRAS(G12C) 3D lung cancer spheroids
title_sort transposable element rna dysregulation in mutant kras(g12c) 3d lung cancer spheroids
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10002638/
https://www.ncbi.nlm.nih.gov/pubmed/36909578
http://dx.doi.org/10.1101/2023.02.27.530369
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