 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 24, 2017 |
| Title |
Gene Expression Profile of ING5-knockdown Brain Tumor Initiating Cell Lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Transcriptome analysis on ING5-knockdown brain tumor stem cell lines
Stem cell-like brain tumor initiating cells (BTICs) cause recurrence of glioblastomas, with BTIC "stemness" affected by epigenetic mechanisms. The ING family of epigenetic regulators (ING1-5) function by targeting histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to the H3K4me3 mark to alter histone acetylation and subsequently, gene expression. Here we find that ectopic expression of ING5, the targeting subunit of HBO1, MOZ and MORF HAT complexes increases expression of the Oct4, Olig2 and Nestin stem cell markers, promotes self-renewal, prevents lineage differentiation and increases stem cell pools in BTIC populations. This activity requires the plant homeodomain region of ING5 that interacts specifically with the H3K4me3 mark. ING5 also enhances PI3K/AKT and MEK/ERK activity to sustain self-renewal of BTICs over serial passage of stem cell-like spheres. ING5 exerts these effects by activating transcription of calcium channel and follicle stimulating hormone (FSH) pathway genes. In silico analyses of The Cancer Genome Atlas (TCGA) data suggest that ING5 is a positive regulator of BTIC stemness, whose expression negatively correlates with patient prognosis, especially in the Proneural and Classical subtypes, and in tumors with low SOX2 expression. These data suggest that altering histone acetylation status and signaling pathways induced by ING5 may provide useful clinical strategies to target tumor resistance and recurrence in glioblastoma.
|
| |
|
| Overall design |
The transcriptome of the shRNA cell line targeting ING5 and the control shRNA cells are compared using Affymetrix GeneChip Human Gene 2.0 ST arrays; two biological replicates for each group are performed.
|
| |
|
| Contributor(s) |
Riabowol K, Wang F |
| Citation(s) |
28925404 |
| Submission date |
Jun 23, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Fangwu Wang |
| E-mail(s) |
fwwang@bccrc.ca
|
| Phone |
17788290550
|
| Organization name |
UBC
|
| Street address |
675 W 10th Ave
|
| City |
Vancouver |
| ZIP/Postal code |
V5Z 1L3 |
| Country |
Canada |
| |
|
| Platforms (1) |
| GPL16686 |
[HuGene-2_0-st] Affymetrix Human Gene 2.0 ST Array [transcript (gene) version] |
|
| Samples (4)
|
|
| Relations |
| BioProject |
PRJNA391568 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE100398_RAW.tar |
31.5 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
|
|
|
|
 |
Less...
More...