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Series GSE124526 Query DataSets for GSE124526
Status Public on Dec 31, 2019
Title A recurrently amplified long noncoding RNA in colorectal cancer regulates p53 protein stability through GRWD1/RPL11/MDM2 axis [RNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary By integrating genome-wide copy number alteration, RNA-seq and proteomics data from 589 colorectal cancer (CRC) patients, we revealed that chromosome 8q24.21 amplification is negatively correlated with p53 protein stability. Using siRNA and CRISPR activation screening, we pinpointed a novel long noncoding gene (PiHL, P53 inHibiting LncRNA) from 8q24.21 as a p53 negative regulator. PiHL is drastically upregulated in CRC and is an independent predictor of CRC poor prognosis. Further In vitro and In vivo models demonstrate that PiHL is crucial in maintaining cell proliferation and inhibiting cell apoptosis through a p53-depedent manner. Mechanistically, PiHL acts to promote p53 ubiquitination by sequestering RPL11 from MDM2, through enhancing GRWD1 and RPL11 complex formation. We further show that p53 can form a feedback loop with PiHL by directly binding to PiHL promoter and regulating its expression. Our study successfully illustrates how cancer cells hijack the PiHL-p53 axis to promote CRC progression and suggests PiHL as a potential therapeutic target in human CRCs.
Overall design We examined gene expression changes in siRNA-NC and siRNA-PiHL treated HCT116 cells using RNA sequencing.
Contributor(s) Deng X, Guan M
Citation(s) 31903119
Submission date Jan 01, 2019
Last update date Apr 13, 2020
Contact name Xuan Deng
Organization name Huashan Hospital
Street address No.512 Huashan Road
City shanghai
ZIP/Postal code 200040
Country China
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (6)
GSM3535849 siRNA-NC_rep1
GSM3535850 siRNA-NC_rep2
GSM3535851 siRNA-NC_rep3
BioProject PRJNA512374
SRA SRP174969

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Supplementary file Size Download File type/resource
GSE124526_siRNA-NC_3_reps_vs._siRNA-PiHL_3_reps.xls.gz 1.2 Mb (ftp)(http) XLS
GSE124526_siRNA-NC_rep1_vs._siRNA-PiHL_rep1.xls.gz 1.1 Mb (ftp)(http) XLS
GSE124526_siRNA-NC_rep2_vs._siRNA-PiHL_rep2.xls.gz 1.1 Mb (ftp)(http) XLS
GSE124526_siRNA-NC_rep3_vs._siRNA-PiHL_rep3.xls.gz 1.1 Mb (ftp)(http) XLS
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