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Series GSE43346 Query DataSets for GSE43346
Status Public on Jun 12, 2013
Title Gene repression with H3K27me3 modification in human small cell lung cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis due to early dissemination and rapid growth. We here analyze gene expression profile of 23 clinical SCLC samples. EZH2 was found to be highly expressed in SCLC samples compared to 42 normal tissues including the normal lung, and other PRC2 members, SUZ12 and EED, were also highly expressed in SCLC. To obtain target genes of PRC2 in SCLC, H3K27me3 mark was mapped in three SCLC cell lines, Lu130, H209 and DMS53, and compared to normal small airway epithelial cells (SAEC). Whereas H3K27me3(+) genes in SAEC were significantly overlapped with PRC-target genes in ES cells (P=1.7x10-31), genes with H3K27me3 in SCLC cell lines but not in SAEC were not significantly overlapped with PRC-target genes in ES cells (P=0.64). These genes with H3K27me3 specifically in SCLC cell lines but not in SAEC showed decreased expression, not only in SCLC cell lines but also in clinical SCLCs, and showed enrichment of GO-terms such as plasma membrane (P=8.1x10-21) and cell adhesion (P=1.7x10-8). Introduction of JUB, a gene showing specific H3K27me3 modification and the strongest repression in the three SCLC cell lines, resulted in repression of cellular growth in DMS53. In clinical SCLC cases, lower JUB level correlated to shorter survival (P=0.002), or a set of PRC target genes (JUB, EPHB4) and marker genes of classic type SCLC (GRP, ASCL1) correlated to shorter survival (P=0.0001) and classified SCLC into two groups with distinct prognosis. Growth of SCLC cell lines was repressed when treated with 3-Deazaneplanocin A, an inhibitor against PRC2. It is suggested that high expression of PRC2 in SCLC contributed to repression of genes including non-PRC-target genes in ES cells, and that the gene repression may play a role in genesis of SCLC.
 
Overall design Gene expression in 23 clinical SCLC samples, 42 normal tissue samples, 3 small cell lung cancer (SCLC) cell lines, and normal small airway epithelial cell (SAEC) was analyzed by Affymetrix arrays.
 
Contributor(s) Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Tanaka Y, Ishikawa Y, Aburatani H
Citation(s) 23714854
Submission date Jan 08, 2013
Last update date Mar 25, 2019
Contact name Atsushi Kaneda
E-mail(s) kaneda@genome.rcast.u-tokyo.ac.jp
Organization name The University of Tokyo
Department RCAST
Lab Genome Science Division
Street address 4-6-1 Komaba
City Meguro-ku
State/province Tokyo
ZIP/Postal code 153-8904
Country Japan
 
Platforms (3)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL97 [HG-U133B] Affymetrix Human Genome U133B Array
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (70)
GSM1060726 Whole_Brain
GSM1060727 Cerebral_cortex
GSM1060728 Pons
This SubSeries is part of SuperSeries:
GSE99316 Gene repression and ChIP-seq in Human Small Cell Lung Cancer
Relations
BioProject PRJNA185493

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
GSE43346_RAW.tar 542.9 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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