Global miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell.

TitleGlobal miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell.
Publication TypeJournal Article
Year of Publication2017
AuthorsKassambara A, Jourdan M, Bruyer A, Robert N, Pantesco V, Elemento O, Klein B, Moreaux J
JournalNucleic Acids Res
Date Published2017 Jun 02
KeywordsCell Differentiation, Cell Transformation, Neoplastic, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Gene Regulatory Networks, Humans, Interferon Regulatory Factors, MicroRNAs, Multiple Myeloma, Plasma Cells, Positive Regulatory Domain I-Binding Factor 1, Repressor Proteins, RNA, Messenger, Transcription Factors, Transcriptional Elongation Factors

MicroRNAs (miRNAs) are small noncoding RNAs that attenuate expression of their mRNA targets. Here, we developed a new method and an R package, to easily infer candidate miRNA-mRNA target interactions that could be functional during a given biological process. Using this method, we described, for the first time, a comprehensive integrated analysis of miRNAs and mRNAs during human normal plasma cell differentiation (PCD). 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 that appear to coordinately regulate multiple members of critical pathways associated with PCD. 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). Furthermore, we found that 24 PCD stage-specific miRNAs are aberrantly overexpressed in multiple myeloma (MM) tumor plasma cells compared to their normal counterpart, suggesting that MM cells frequently acquired expression changes in miRNAs already undergoing dynamic expression modulation during normal PCD. Altogether, our analysis identifies candidate novel key miRNAs regulating networks of significance for normal PCD and malignant plasma cell biology.

Alternate JournalNucleic Acids Res.
PubMed ID28459970
PubMed Central IDPMC5449613