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Series GSE138606 Query DataSets for GSE138606
Status Public on Dec 11, 2019
Title Long non-coding RNA RP11-19E11.1 is an E2F1 target required for tumor cell proliferation and survival in basal breast cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Long non-coding RNAs (lncRNAs) play key roles in the regulation of breast cancer initiation and progression. LncRNAs are differentially expressed in breast cancer subtypes. Basal-like breast cancers are generally poorly differentiated tumors, are enriched in embryonic stem cell signatures, lack expression of estrogen receptor, progesterone receptor, and HER2 (triple negative breast cancer, TNBC), and show activation of proliferation-associated factors. We hypothesized that lncRNAs are key regulators of basal breast cancers. Using The Cancer Genome Atlas we identified lncRNAs that are overexpressed in basal tumors compared to other breast cancer subtypes and expressed in at least 10% of patients. Remarkably, we identified lncRNAs whose expression correlated with patient prognosis. We then evaluated the function of a subset of lncRNA candidates in the oncogenic process in vitro. Here, we report the identification and characterization of the chromatin-associated lncRNA, RP11-19E11.1, which is up-regulated in 40% of basal primary breast cancers. Gene set enrichment analysis in primary tumors and in cell lines uncovered a correlation between RP11-19E11.1 expression level and the E2F oncogenic pathway. We show that this lncRNA is chromatin-associated and an E2F1 target, and its expression is necessary for cancer cell proliferation and survival. Finally, we used lncRNA expression levels as a tool for drug discovery in vitro, identifying Protein Kinase C (PKC) as a potential therapeutic target for a subset of basal-like breast cancers. Our findings suggest lncRNA overexpression is clinically relevant. Understanding deregulated lncRNA expression in basal-like breast cancer may lead to potential prognostic and therapeutic applications.
 
Overall design RNA-seq data from HCC38, MDA-MB-468 and SUM149PT was obtained in duplicate after RP11-19E11.1 KD.
 
Contributor(s) Giro-Perafita A, Khodadadi-Jamayran A, Tsirigos A, Sanchez I, Esteva FJ
Citation(s) 31934613
Submission date Oct 08, 2019
Last update date Mar 11, 2020
Contact name Alireza Khodadadi-Jamayran
Organization name New York University, NYU Langone Medical Center
Department Division of Advanced Research Technologies (DART)
Lab Applied Bioinformatics Laboratories (ABL)
Street address 550 1st Ave, MSB 304
City New York City
State/province NY
ZIP/Postal code 10016
Country USA
 
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (12)
GSM4114185 MDA-MB-468 LNA NS R1
GSM4114186 MDA-MB-468 RP19 KD R1
GSM4114187 MDA-MB-468 LNA NS R2
Relations
BioProject PRJNA576500
SRA SRP224820

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

Supplementary file Size Download File type/resource
GSE138606_RAW.tar 1.6 Gb (http)(custom) TAR (of BW, TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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