We focused our attention on miRNAs already found upregulated in SSc such as miR-21-5p, miR-92a-3p, and on miR-155-5p, miR 126-3p and miR-16-5p known to be deregulated in malignancies associated to SSc, i.e., breast, lung, and hematological malignancies. miR-21-5p, miR-92a-3p, miR-155-5p, and miR-16-5p expression was significantly higher in SSc sera compared to healthy controls.
Although further studies are necessary to determine the underlying apoptotic pathway, we propose that inhibition of miR-21 in dermal fibroblasts from lesional skin may be useful in harnessing progressive fibrosis in SSc.
Finally, DNA demethylation of regulatory genes (eNOS, CD40L and CD70), therapeutic effects associated with Trichostatin A (TSA) treatment, and abnormal expression of a large spectrum of microRNAs (miR-21, -31, -146, -503, -145, -29b, etc.) are all observed in SSc.
We also found the combination of serum levels of miR-206 and miR-21 was more useful in distinguishing patients with scleroderma from normal subjects than either miR-206 or miR-21 alone.
MiR-21 may function in an amplifying circuit to enhance TGF-β signaling events in SSc fibrosis, and suggesting that miR-21 may act as a potential therapeutic target.