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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 05, 2022 |
| Title |
Multi-hallmark long noncoding RNA maps reveal non-small cell lung cancer vulnerabilities [CRISPRseries] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Long noncoding RNAs (lncRNAs) are widely dysregulated in cancer, yet their functional roles in cellular disease hallmarks remain unclear. Here we employ pooled CRISPR deletion to perturb 831 lncRNAs detected in KRAS-mutant non-small cell lung cancer (NSCLC), and measure their contribution to proliferation, chemoresistance and migration across two cell backgrounds. Integrative analysis of this data outperforms conventional “dropout” screens in identifying cancer genes, while prioritising disease-relevant lncRNAs with pleiotropic and background-independent roles. Altogether 80 high-confidence oncogenic lncRNAs are active in NSCLC, the majority identified here for the first time, and which tend to be amplified and overexpressed in tumours. A follow-up antisense oligonucleotide (ASO) screen shortlisted two candidates, Cancer Hallmarks in Lung LncRNA 1 (CHiLL 1) and GCAWKR, whose knockdown consistently suppressed cancer hallmarks in a variety of two- and three-dimension tumour models. Molecular phenotyping reveals that CHiLL 1 and GCAWKR control cellular-level phenotypes via distinct transcriptional networks converging on common oncogenic pathways. In summary, this work reveals a multi-dimensional functional lncRNA landscape underlying NSCLC that contains potential therapeutic vulnerabilities.
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| Overall design |
High-throughput CRISPR/Cas9-deletion screens using a long noncoding RNA targeting paired-guide RNA library in two KRAS+ non-small cell lung cancer models, A549 and NCI-H460, performing proliferation, cisplatin drug response and migration based assays.
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| Contributor(s) |
Esposito R, Polidori T, Meise DF, Pulido-Quetglas C, Chouvardas P, Forster S, Schaerer P, Kobel A, Schlatter J, Kerkhof E, Roemmele M, Westemeier ES, Zhu L, Lanzós A, Guillen-Ramirez HA, Basile G, Carrozzo I, Vancura A, Ullrich S, Andrades A, Harvey D, Medina PP, Ma PC, Haefliger S, Wang X, Martinez I, Ochsenbein A, Riether C, Johnson R |
| Citation(s) |
36778670 |
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https://www.sciencedirect.com/science/article/pii/S2666979X22001136
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| Submission date |
Jun 29, 2022 |
| Last update date |
Feb 24, 2023 |
| Contact name |
Rory Johnson |
| E-mail(s) |
rory.johnson@ucd.ie
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| Phone |
+353851840699
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| Organization name |
UCD Conway Institute for Biomolecular and Biomedical Research
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| Street address |
Belfield
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| City |
Dublin |
| ZIP/Postal code |
D04 V1W8 |
| Country |
Ireland |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (29)
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| This SubSeries is part of SuperSeries: |
| GSE207229 |
Multi-hallmark long noncoding RNA maps reveal non-small cell lung cancer vulnerabilities. |
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| Relations |
| BioProject |
PRJNA854197 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE207228_A549Library_pgRNAdesigns.xlsx |
1.3 Mb |
(ftp)(http) |
XLSX |
| GSE207228_A549_cis_DeathvsT0.txt.gz |
34.6 Kb |
(ftp)(http) |
TXT |
| GSE207228_A549_cis_T3_25uMvsT0.txt.gz |
34.9 Kb |
(ftp)(http) |
TXT |
| GSE207228_A549_cis_T3_6.5uMvsT0.txt.gz |
36.8 Kb |
(ftp)(http) |
TXT |
| GSE207228_A549_counts_table.txt.gz |
330.6 Kb |
(ftp)(http) |
TXT |
| GSE207228_A549_mig_NMvsMIG.txt.gz |
36.8 Kb |
(ftp)(http) |
TXT |
| GSE207228_A549_pro_CFSE_HvsL.txt.gz |
34.9 Kb |
(ftp)(http) |
TXT |
| GSE207228_A549_pro_T3vsT0.txt.gz |
36.4 Kb |
(ftp)(http) |
TXT |
| GSE207228_H460_counts_table.txt.gz |
200.1 Kb |
(ftp)(http) |
TXT |
| GSE207228_H460_pro_CFSE_HvsL.txt.gz |
35.6 Kb |
(ftp)(http) |
TXT |
| GSE207228_H460_pro_T3vsT0.txt.gz |
35.9 Kb |
(ftp)(http) |
TXT |
| GSE207228_Migration_counts_table.txt.gz |
121.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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