MicroRNAs in B-cell lymphomas: how a complex biology gets more complex
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't, Review
PubMed
25541152
DOI
10.1038/leu.2014.351
PII: leu2014351
Knihovny.cz E-resources
- MeSH
- Apoptosis MeSH
- Lymphoma, B-Cell genetics metabolism MeSH
- Gene Deletion MeSH
- Humans MeSH
- MicroRNAs metabolism MeSH
- Mice MeSH
- NF-kappa B p50 Subunit metabolism MeSH
- DNA Damage MeSH
- Receptors, Antigen, B-Cell metabolism MeSH
- Gene Expression Regulation, Neoplastic * MeSH
- Signal Transduction MeSH
- Gene Expression Profiling MeSH
- Neoplasm Transplantation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- MicroRNAs MeSH
- MIRN150 microRNA, human MeSH Browser
- MIRN155 microRNA, human MeSH Browser
- MIRN21 microRNA, human MeSH Browser
- MIRN34 microRNA, human MeSH Browser
- NF-kappa B p50 Subunit MeSH
- NFKB1 protein, human MeSH Browser
- Receptors, Antigen, B-Cell MeSH
MicroRNAs (miRNAs) represent important regulators of gene expression besides transcriptional control. miRNA regulation can be involved in the cell developmental fate decisions, but can also have more subtle roles in buffering stochastic fluctuations in gene expression. They participate in pathways fundamental to B-cell development like B-cell receptor (BCR) signalling, B-cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of immunoglobulins. miRNAs influence B-cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and memory B cells. In this review, we discuss miRNAs with essential functions in malignant B-cell development (such as miR-150, miR-155, miR-21, miR-34a, miR-17-92 and miR-15-16). We also put these miRNAs in the context of normal B-cell differentiation, as this is intimately connected to neoplastic B-cell development. We review miRNAs' role in the most common B-cell malignancies, including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL). We focus on miR-contribution to the regulation of important signalling pathways (such as NF-κB, PI3K/AKT and TGF-β), BCR signalling and its modulators (such as PTEN, SHIP-1, ZAP-70, GAB1 and BTK), anti- and pro-apoptotic proteins (such as BCL2, MCL1, TCL1, BIM, p53 and SIRT1) and transcription factors (such as MYC, MYB, PU.1, FOXP1 and BCL6). We also discuss the association of miRNAs' expression levels with the patients' survival and response to therapy, summarizing their potential use as predictive and prognostic markers. Importantly, the targeting of miRNAs (like use of anti-miR-155 or miR-34a mimic) could provide a novel therapeutic approach as evidenced by tumour regression in xenograft mouse models and initial promising data from clinical trials.
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