Reciprocal modulation of Linc-223 and its ligand miR-125a on the basis of platelet function level. (25th November 2020) - De Rosa, S
Abstract: Background: Cardiovacular diseases (CVD) are the leading cause of death worldwide. Platelet play a key role in the pathophysiology of multiple CVD. LincRNAs are long non-coding RNAs transcribed from intergenic DNA segments. Some members of this class were recently associated with human disease. Linc-223 is co-transcribed together with mir-223 and was recently shown to bind to miR-125. Both miR-223 and miR-125 are highly expressed in platelets. Purpose: In light of the capability of Linc-223 to bind to miR-125, we aimed to investigate whether their reciprocal expression levels might reflect the degree of platelet activity. Methods: RNA was extracted using miRVANA. MiRNAs and lncRNAs were measured by means of quantitative Real Time RT-PCR. Results: We found a significant reduction of Linc-223 levels (p<0.05) along with a significant increase in miR-125 levels (p<0.05) after initiation of any antiplatelet treatment (n=30) compared to naïve patients (n=10). Moreover, the upgrade to a higher-intensity antiplatelet treatment with ASA+ticagrelor from ASA+clopidogrel (n=30) was associated to a further down-regulation of Linc-223 (p<0.05) along with a further increase of miR-125. (p<0.05). Finally, these results were validated in a larger cohort of 300 patients from the ATLANTIS study, demonstrating significant modulation of both miR-223 and miR-125 in patients with high on-treatment platelet aggregation levels compared to antiplatelet-responsive patients. Conclusions: We identify a reciprocal modulation of Linc-223 and miR-125, its ligand upon different levels of platelet aggregations. These results are compatible with previous evidence from patients with Acute Myeloid Leukemia, that Linc-223 might bind to and sponge miR-125, inhibiting its effect. These results suggest that plasma levels of Linc-223, miR-125 and miR-223 might be used a biomarkers of platelet finction in a clinical context, for risk stratification of patients or to assess the responsiveness to antiplatelet treatments. Funding Acknowledgement: Type of funding source: None