MicroRNAs, The Immune System and Rheumatic Disease

Esmerina Tili; Jean-Jacques Michaille; Stefan Costinean; Carlo M. Croce


Nat Clin Pract Rheumatol. 2008;4(10):534-541. 

In This Article


miRNAs have important roles in fundamental cellular processes, and their dysregulated expression is observed in all the pathological conditions examined so far. The functional activities of hematopoietic cells are clearly regulated not only by the balanced expression of genes encoding cytokines, transcription factors or other regulatory proteins, but also by miRNAs and, most probably, other noncoding transcripts that are yet to be defined. miRNAs crucial for the differentiation and function of immune cells have been found to be abnormally expressed in both solid and nonsolid tumors; analyses of 'hematopoietic-specific' miRNAs, such as miR-142, miR-155, miR-181 and miR-223, in malignant hematopoietic cell lines showed that, although they have a similar pattern of expression to that observed in normal cell lineages, their levels of expression were significantly altered. This observation indicates that these miRNAs are involved in hematological malignancies.[52] Many studies have shown that a history of inflammation or autoimmune disease increases the risk of cancer. Accordingly, the expression of all the above-mentioned miRNAs results in defects in central and peripheral tolerance. It is logical, therefore, to consider these miRNAs as potential links between inflammation, autoimmunity and tumorigenesis. The characterization of signaling cascades that control the expression of miRNAs in hematopoietic lineages, as well as the understanding of how miRNAs can modulate the expression of components of these signaling pathways, is a matter of great interest. The use of anti-miRNA, or mimic-miRNA oligonucleotides have been tested in different cancer cell lines,[7] in mice[7] and in nonhuman primates.[53] These investigations have already shown that miRNA-based gene therapies targeting dysregulated miRNAs have the potential for becoming therapeutic tools of choice for the treatment of metabolic disorders, cancers and immune-related diseases. It will be very interesting to see if these miRNA-based gene therapies will be used to treat patients with rheumatic disease, such as RA, in the near future.

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