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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 02, 2012 |
| Title |
Protein Arginine Methyltransferase 6 dependent gene expression and splicing: Association with breast cancer outcomes |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Protein arginine methyltransferase-6 (PRMT6) regulates steroid-dependent transcription and alternative splicing, and is implicated in endocrine system development and function, cell death, cell cycle, gene expression and cancer. Despite its role in these processes, little is known about its function and cellular targets in breast cancer. To identify novel gene targets regulated by PRMT6 in breast cancer cells, we used a combination of small interfering RNA (siRNA) and exon-specific microarray profiling in vitro, coupled to in vivo validation in normal breast and primary human breast tumours. This approach, which allows the examination of genome-wide changes in individual exon usage and total transcript levels, demonstrated PRMT6 knockdown significantly affected: (i) the transcription of 159 genes, and (ii) alternate splicing of 449 genes. Importantly, the levels of PRMT6 itself were significantly decreased in breast cancer, relative to normal breast tissue. The PRMT6 dependent transcriptional and alternative splicing targets identified in vitro, were validated in human breast tumours. Notably, expression of PRMT6 and the corresponding gene signature, correlated with decreased probability of relapse-free or distant metastasis free survival in ER+ breast cancer. These results suggest that dysregulation of PRMT6 dependent transcription and alternative splicing may be involved in breast cancer pathophysiology and the molecular consequences identifying a unique and informative biomarker profile.
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| Overall design |
Total RNA obtained from MCF7 breast cancer cells transfected with siRNA directed against PRMT6 or negative control siRNA (Ambion Silencer Select negative control).
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| Contributor(s) |
Dowhan DH, Harrison MJ, Eriksson N, Bailey P, Pearen MA, Fuller PJ, Funder JW, Simpson ER, Leedman PJ, Tilley WD, Brown MA, Clarke CL, Muscat GE |
| Citation(s) |
22673335 |
| Submission date |
Mar 15, 2012 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Michael Andrew Pearen |
| E-mail(s) |
m.pearen@uq.edu.au
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| Phone |
+61 7 33462365
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| Fax |
+61 7 33462101
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| Organization name |
Institute for Molecular Bioscience
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| Lab |
Group Muscat
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| Street address |
The University of Queensland
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| City |
St Lucia |
| State/province |
Queensland |
| ZIP/Postal code |
4072 |
| Country |
Australia |
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| Platforms (1) |
| GPL5175 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [transcript (gene) version] |
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| Samples (12)
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| GSM896558 |
MCF7 with siRNA against PRMT6, biological Rep1 |
| GSM896568 |
MCF7 with siRNA against PRMT6, biological Rep2 |
| GSM896569 |
MCF7 with siRNA against PRMT6, biological Rep3 |
| GSM896570 |
MCF7 with siRNA against PRMT6, biological Rep4 |
| GSM896571 |
MCF7 with siRNA against PRMT6, biological Rep5 |
| GSM896572 |
MCF7 with siRNA against PRMT6, biological Rep6 |
| GSM896573 |
MCF7 with negative control siRNA, biological Rep1 |
| GSM896574 |
MCF7 with negative control siRNA, biological Rep2 |
| GSM896575 |
MCF7 with negative control siRNA, biological Rep3 |
| GSM896576 |
MCF7 with negative control siRNA, biological Rep4 |
| GSM896577 |
MCF7 with negative control siRNA, biological Rep5 |
| GSM896578 |
MCF7 with negative control siRNA, biological Rep6 |
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| Relations |
| BioProject |
PRJNA153415 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE36542_RAW.tar |
241.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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