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Series GSE120566 Query DataSets for GSE120566
Status Public on Jul 19, 2022
Title Mutant KRAS regulates transposable element RNA and innate immunity via KRAB zinc-finger genes
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary RAS genes are the most frequently mutated oncogenes in cancer, yet the effects of oncogenic RAS signaling on the noncoding transcriptome remain unclear. We analyzed the transcriptomes of human airway and bronchial epithelial cells transformed with mutant KRAS to define the landscape of KRAS-regulated noncoding RNAs. We found that oncogenic KRAS signaling upregulates noncoding transcripts throughout the genome, many of which arise from transposable elements (TEs). These TE RNAs exhibit differential expression, are preferentially released in extracellular vesicles, and are regulated by KRAB zinc-finger (KZNF) genes, which are broadly downregulated in mutant KRAS cells and lung adenocarcinomas in vivo. Moreover, mutant KRAS induces the epigenetic reprogramming of IFN-stimulated genes (ISGs), some of which are also regulated by KZNFs. Our results reveal that mutant KRAS remodels the noncoding transcriptome via KZNF-mediated epigenomic reprogramming, revealing the broad scope of intracellular and extracellular RNAs regulated by this oncogenic signaling pathway.
Overall design Comparative gene expression analysis of cell lines (6x AALE and 6x HBEC) expressing mutant KRAS (3x G12D and 3x G12V, resp) and extracellular vesicles secreted from AALE (6x).
Contributor(s) Reggiardo RE, Brooks A, Kim DH
Citation(s) 35858545
NIH grant(s)
Grant ID Grant title Affiliation Name
F99 DK131504 Cell free RNA liquid biopsies UNIVERSITY OF CALIFORNIA SANTA CRUZ Roman Reggiardo
Submission date Sep 27, 2018
Last update date Nov 29, 2022
Contact name Daniel Kim
Organization name UC Santa Cruz
Department Biomolecular Engineering
Street address McLaughlin Dr
City Santa Cruz
State/province California
ZIP/Postal code 95060
Country USA
Platforms (3)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (20)
GSM6216323 AALE, pBABE control, ATAC
GSM6216324 AALE, pBABE control, RNA, 1 [intra.aale.1.ctrl]
BioProject PRJNA493581
SRA SRP162736

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE120566_RAW.tar 473.4 Mb (http)(custom) TAR (of BIGWIG) 863.4 Kb (ftp)(http) CSV
GSE120566_aale_exo_gencode+rmsk_norm_counts.csv.gz 1.1 Mb (ftp)(http) CSV
GSE120566_aale_exo_gencode_norm_counts.csv.gz 1.7 Mb (ftp)(http) CSV
GSE120566_aale_intra_gencode+rmsk_norm_counts.csv.gz 1.0 Mb (ftp)(http) CSV
GSE120566_aale_intra_gencode_norm_counts.csv.gz 2.1 Mb (ftp)(http) CSV
GSE120566_exo.EditingIndex.csv.gz 26.0 Kb (ftp)(http) CSV 1.1 Mb (ftp)(http) CSV 825.7 Kb (ftp)(http) CSV
GSE120566_hbec_intra_gencode+rmsk_norm_counts.csv.gz 1.1 Mb (ftp)(http) CSV
GSE120566_hbec_intra_gencode_norm_counts.csv.gz 2.2 Mb (ftp)(http) CSV 50.7 Kb (ftp)(http) CSV
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Raw data are available in SRA
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Processed data provided as supplementary file

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