| Popis |
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, miR-15-16). We also put these miRNAs in the context of normal B cell differentiation, since 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 (like NF-KB, PI3K/AKT, TGF-beta), BCR signalling and its modulators (like PTEN, SHIP-1, ZAP-70, GAB1, BTK), anti- and pro-apoptotic proteins (like BCL2, MCL1, TCL1, BIM, p53, SIRT1), and transcription factors (like MYC, MYB, PU.1, FOXP1, 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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