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GEO help: Mouse over screen elements for information. |
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| 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
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| 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.
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| 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).
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| 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 |
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| Submission date |
Sep 27, 2018 |
| Last update date |
Nov 29, 2022 |
| Contact name |
Daniel Kim |
| E-mail(s) |
daniel.kim@ucsc.edu
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| Organization name |
UC Santa Cruz
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| Department |
Biomolecular Engineering
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| Street address |
McLaughlin Dr
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| City |
Santa Cruz |
| State/province |
California |
| ZIP/Postal code |
95060 |
| Country |
USA |
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| Platforms (3) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (20)
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| GSM6216325 |
AALE, KRASG12D, RNA, 1 [intra.aale.1.kras] |
| GSM6216326 |
AALE, pBABE control, RNA, 2 [intra.aale.2.ctrl] |
| GSM6216327 |
AALE, KRASG12D, RNA, 2 [intra.aale.2.kras] |
| GSM6216328 |
AALE, pBABE control, RNA, 3 [intra.aale.3.ctrl] |
| GSM6216329 |
AALE, KRASG12D, RNA, 3 [intra.aale.3.kras] |
| GSM6216330 |
HBEC, KRASG12V, RNA, 1 [intra.hbec.1.wt2_kras_v12] |
| GSM6216331 |
HBEC, LACZ, RNA, 1 [intra.hbec.1.wt2_lacz] |
| GSM6216332 |
HBEC, KRASG12V, RNA, 2 [intra.hbec.2.wt2_kras_v12] |
| GSM6216333 |
HBEC, LACZ, RNA, 2 [intra.hbec.2.wt2_lacz] |
| GSM6216334 |
HBEC, KRASG12V, RNA, 3 [intra.hbec.3.wt2_kras_v12] |
| GSM6216335 |
HBEC, LACZ, RNA, 3 [intra.hbec.3.wt2_lacz] |
| GSM6216336 |
exo AALE, pBABE control, RNA, 1 [rnaEASY.aale.1.ctrl] |
| GSM6216337 |
exo AALE, KRASG12D, RNA, 1 [rnaEASY.aale.1.kras] |
| GSM6216338 |
exo AALE, pBABE control, RNA, 2 [rnaEASY.aale.2.ctrl] |
| GSM6216339 |
exo AALE, KRASG12D, RNA, 2 [rnaEASY.aale.2.kras] |
| GSM6216340 |
exo AALE, pBABE control, RNA, 3 [rnaEASY.aale.3.ctrl] |
| GSM6216341 |
exo AALE, KRASG12D, RNA, 3 [rnaEASY.aale.3.kras] |
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| Relations |
| BioProject |
PRJNA493581 |
| SRA |
SRP162736 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE120566_RAW.tar |
473.4 Mb |
(http)(custom) |
TAR (of BIGWIG) |
| GSE120566_aale.kras.v.ctrl.de-seq.csv.gz |
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 |
| GSE120566_exo.gencode.kras.v.ctrl.de-seq.csv.gz |
1.1 Mb |
(ftp)(http) |
CSV |
| GSE120566_ha1em.kras.v.ctrl.de-seq.csv.gz |
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 |
| GSE120566_te.locus.aale.kras.v.ctrl.de-seq.csv.gz |
50.7 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
| Processed data provided as supplementary file |
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