Reciprocal modulation of Linc-223 and its ligand miR-125a on the basis of platelet function level
Reciprocal modulation of Linc-223 and its ligand miR-125a on the basis of platelet function level
复制标题
基于血小板功能水平的 Linc-223 及其配体 miR-125a 的相互调节
DOI：
10.1093/ehjci/ehaa946.3760
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发表时间：
2020
影响因子：
39.3
通讯作者：
C. Indolfi
中科院分区：
文献类型：
--
作者：
S. D. Rosa;S. L. Bella;G. Canino;J. Siller;C. Eyleten;M. Postuła;Laura Tammè;C. Iaconetti;J. Sabatino;A. Polimeni;S. Sorrentino;C. Gareri;L. Proto;A. Strangio;C. Indolfi
心血管疾病（CVD）是全球死亡的主要原因。血小板在多发性CVD的病理生理学中起关键作用。LincRNA是从基因间DNA片段转录的长的非编码RNA。这个类别的一些成员最近与人类疾病有关。Linc-223与mir-223一起共转录，最近显示与miR-125结合。miR-223和miR-125均在血小板中高度表达。
鉴于Linc-223与miR-125结合的能力，我们旨在研究它们的相互表达水平是否可以反映血小板活性的程度。
使用miRVANA提取RNA。通过定量真实的时间RT-PCR测量miRNA和lncRNA。
我们发现，与初治患者（n=10）相比，在开始任何抗血小板治疗（n=30）后，Linc-223水平显著降低（p <0.05）沿着miR-125水平显著升高（p<0.05）。此外，从阿萨+氯吡格雷（n=30）升级为更高强度的ASA+替格瑞洛抗血小板治疗与Linc-223的进一步下调（p<0.05）以及miR-125的进一步增加沿着。（p<0.05）。最后，这些结果在来自ATLANTIS研究的300名患者的更大队列中得到验证，证明与抗血小板应答患者相比，治疗中血小板聚集水平高的患者中miR-223和miR-125均显著调节。
我们确定了Linc-223和miR-125（其配体）对不同水平血小板聚集的相互调节。这些结果与先前来自急性髓性白血病患者的证据一致，即Linc-223可能结合并吸收miR-125，抑制其作用。这些结果表明，Linc-223、miR-125和miR-223的血浆水平可用作临床背景下血小板功能的生物标志物，用于患者的风险分层或评估抗血小板治疗的反应性。
资金来源类型：无
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.
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.
RNA was extracted using miRVANA. MiRNAs and lncRNAs were measured by means of quantitative Real Time RT-PCR.
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.
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.
Type of funding source: None