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

ABSTRACT: 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.

SUBMITTER: Kassambara A

PROVIDER: S-EPMC5449613 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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

Kassambara Alboukadel A Jourdan Michel M Bruyer Angélique A Robert Nicolas N Pantesco Véronique V Elemento Olivier O Klein Bernard B Moreaux Jérôme J

Nucleic acids research 20170601 10

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 expr ...[more]

PMID: 28459970

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Project description:BackgroundThe distinction between right-sided and left-sided colon adenocarcinoma has recently received considerable. This study aims to identify key MicroRNA (miRNA) and mRNAs in right-sided colon adenocarcinoma (RSCOAD) and left-sided colon adenocarcinoma (LSCOAD) by TCGA integration analysis.MethodsThe miRNA and mRNA expression profiles of a large group of patients with RSCOAD and LSCOAD were obtained from TCGA. The differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were identified by TCGA integration analysis. The optimal diagnostic miRNA biomarkers for RSCOAD and LSCOAD were identified by Boruta algorithm. We established classification models to distinguish RSCOAD and LSCOAD. Protein-protein interaction (PPI) network analysis, DEmiRNA-DEmRNA interaction analysis, and functional annotation were performed. The expression of selected DEmiRNAs and DEmRNAs was validated by qRT-PCR.ResultsA total of 2534 DEmRNAs (940 downregulated and 1594 upregulated mRNAs) and 54 DEmiRNAs (22 downregulated and 32 upregulated miRNAs) between RSCOAD and LSCOAD were identified. The feature selection procedure was to obtain 22 optimal diagnostic miRNAs biomarkers in RSCOAD compared to LSCOAD. The AUC of the random forests model was 0.869 and the specificity and sensitivity of this model were 79% and 84.6%, respectively. Three DEmiRNAs (hsa-miR-224-5p, hsa-miR-155-5p, and hsa-miR-31-5p) and five DEmRNAs (CXCR4, SMAD4, KRAS, FITM2, and PLAGL2) were identified key DEmiRNAs and DEmRNAs in RSCOAD compared to LSCOAD. The qRT-PCR results of CXCR4, FITM2, TFAP2A, ULBP2, hsa-miR-224-5p, and hsa-miR-155-5p were consistent with our integrated analysis.ConclusionA total of three DEmiRNAs (hsa-miR-224-5p, hsa-miR-155-5p, and hsa-miR-31-5p) and five DEmRNAs (CXCR4, SMAD4, KRAS, FITM2, and PLAGL2) may be involved in the pathogenesis of RSCOAD and LSCOAD which may make a contribution for understanding mechanisms and developing therapeutic strategies for RSCOAD and LSCOAD.

Dataset Information

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

Publications

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

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