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| 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
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| 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.
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| 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.
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| Contributor(s) |
Sato T, Kaneda A, Tsuji S, Isagawa T, Yamamoto S, Fujita T, Tanaka Y, Ishikawa Y, Aburatani H |
| Citation(s) |
23714854 |
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| 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
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| Organization name |
The University of Tokyo
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| Department |
RCAST
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| Lab |
Genome Science Division
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| Street address |
4-6-1 Komaba
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| City |
Meguro-ku |
| State/province |
Tokyo |
| ZIP/Postal code |
153-8904 |
| Country |
Japan |
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| 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 |
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| Samples (70)
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| This SubSeries is part of SuperSeries: |
| GSE99316 |
Gene repression and ChIP-seq in Human Small Cell Lung Cancer |
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| Relations |
| BioProject |
PRJNA185493 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43346_RAW.tar |
542.9 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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