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| Status |
Public on Jun 23, 2017 |
| Title |
Global miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell |
| Platform organism |
synthetic construct |
| Sample organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Background: MicroRNAs (miRNAs) are small noncoding RNAs that attenuate expression of their mRNA targets. miRNAs have been involved in fine-tuning critical biological processes, but the potential contribution of miRNAs to human plasma cell differentiation (PCD) has remained largely unknown.
Methods: We analyzed the expression profile of miRNAs and mRNAs during PCD. We developed a method and R package, to infer candidate miRNA-mRNA target interactions that could be active and functional in PCD. Finally, we experimentally validated biologically relevant miRNA – mRNA networks.
Results: Our results reveal 63 miRNAs with significant temporal changes in their expression during normal PCD. We derived a high-confidence network of 295 target relationships comprising 47 miRNAs and 141 targets. These relationships include new examples of miRNAs (miR-30, miR-106b and miR-16) that appear to coordinately regulate multiple members of critical pathways associated with PCD, including IRF4/PRDM1 axis, TGF-b pathway, autophagy, ZBTB4/EZH2 axis and cell cycle. Consistent with this, we have experimentally validated a role for the miRNA-30b/c/d-mediated regulation of key PCD factors (IRF4, PRDM1, ELL2 and ARID3A), which expression was altered significantly upon transfection of pre-miRNA-30 or anti-miR-30 oligunucleotides. Furthermore, we found that 24 PCD stage-specific miRNAs are aberrantly overexpressed in multiple myeloma (MM) tumor cells compared to their normal counterpart and/or are associated with high risk myeloma, suggesting that MM cells frequently acquired expression changes in miRNAs already undergoing dynamic expression modulation during normal PCD.
Conclusions: Our comprehensive analysis of normal PCD miRNome identifies candidate novel key miRNAs regulating networks of significance for normal PCD and malignant plasma cell biology.
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| Overall design |
Global miRNA expression profiling was carried out for in vitro human plasma cell differentiation cell subpopulations, including memory B cells, preplasmablasts, plasmablasts and plasma cells.
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| Contributor(s) |
Kassambara A, Jourdan M, Bruyer A, Robert N, Pantesco V, Elemento O, Klein B, Moreaux J |
| Citation(s) |
28459970 |
| Submission date |
Sep 08, 2016 |
| Last update date |
Jun 23, 2017 |
| Contact name |
Jerome Moreaux |
| E-mail(s) |
jerome.moreaux@igh.cnrs.fr
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| Organization name |
CHRU Montpellier
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| Department |
Biological Hematology
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| Lab |
Laboratory for Monitoring Innovative Therapies
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| Street address |
80 Av. Augustin Fliche
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| City |
Montpellier |
| ZIP/Postal code |
34295 |
| Country |
France |
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| Platforms (1) |
| GPL8786 |
[miRNA-1] Affymetrix Multispecies miRNA-1 Array |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA342352 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE86604_RAW.tar |
3.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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