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| Status |
Public on Jan 10, 2017 |
| Title |
EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions [mRNA expression] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Multiple Myeloma (MM) is a plasma cell tumor localized to the bone marrow (BM). Despite current progress in improving patient outcome, MM remains largely incurable. Disease clonal and interpatient heterogeneity has hampered identification of a common underlying mechanism for disease establishment and have slowed the development of novel targeted therapies. Epigenetic aberrations are now emerging as increasingly important in tumorigenesis, thus selective targeting of crucial epigenetic enzymes may provide new therapeutic potential in cancer including MM. Recently, we and others suggested the histone methyltransferase enhancer of zeste homolog 2 (EZH2), to be a potential therapeutic target in MM. Now we show that pharmacological inhibition of EZH2 suppresses the MM cell growth through downregulation of MM-associated oncogenes; IRF-4, XBP-1, PRDM1/BLIMP-1and c-MYC. We also show that downregulation of these genes is mediated via reactivated expression of microRNAs with tumor suppressor functions; primarily miR125a-3p and miR320c. Using chromatin immunoprecipitation (ChIP) we demonstrate that miR125a-3p and miR320c are targets of EZH2 and H3K27me3 in MM cell lines and primary MM cells. Our results further highlight the importance of polycomb-mediated silencing in MM to include microRNAs with tumor suppressor activity. This novel role further strengthens the oncogenic features of EZH2 and its potential as a therapeutic target in MM.
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| Overall design |
6 samples (3 biological replicates) were used in this analysis. The pairwise comparision of Inactive drug (UNC2400) wth the active drug (UNC1999) was made for each biological replicate.The anti-myeloma effects exerted by EZH2 inhibition was investigated using UNC1999, small specific inhibitor of EZH2, at 120 hours post-treament by analyzing global changes in mRNA and miRNA expression
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| Contributor(s) |
Alzrigat M, Agarwal P |
| Citation(s) |
28052011 |
| Submission date |
Oct 06, 2016 |
| Last update date |
Jan 11, 2017 |
| Contact name |
Prasoon Agarwal |
| E-mail(s) |
helena.jernberg_wiklund@igp.uu.se
|
| Organization name |
Rudbeck Laboratory, Uppsala University
|
| Department |
IGP
|
| Street address |
Dag Hammarshkojlds vag 20
|
| City |
Uppsala |
| State/province |
Sweden |
| ZIP/Postal code |
75185 |
| Country |
Sweden |
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| Platforms (1) |
| GPL17585 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [probe set (exon) version] |
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| Samples (6)
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| GSM2339213 |
INA-6 treated with control UNC2400, biological repl 1 |
| GSM2339214 |
INA-6 treated with EZH2 inhibitor UNC1999, biological repl 1 |
| GSM2339215 |
INA-6 treated with control UNC2400, biological repl 2 |
| GSM2339216 |
INA-6 treated with EZH2 inhibitor UNC1999, biological repl 2 |
| GSM2339217 |
INA-6 treated with control UNC2400, biological repl 3 |
| GSM2339218 |
INA-6 treated with EZH2 inhibitor UNC1999, biological repl 3 |
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| This SubSeries is part of SuperSeries: |
| GSE87716 |
EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions |
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| Relations |
| BioProject |
PRJNA345623 |
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