Platelet miR-107 Participates in Clopidogrel Resistance after PCI Treatment by Regulating P2Y12

Introduction: High platelet reactivity (HPR) caused by clopidogrel tolerance is an adverse reaction of acute coronary syndrome (ACS) patients who receive clopidogrel antiplatelet therapy after percutaneous coronary intervention (PCI) surgery. Platelet microRNA (miRNA) is related to platelet reactivity. This study explored the mechanism of platelet miRNA in regulating platelet reactivity. Methods: We recruited 50 ACS/PCI patients and divided them into the HPR group (P2Y12 reaction units [PRU] >= 300) and the LPR group (PRU < 170) according to the PRU through the VerifyNow P2Y12 assay. P2Y12-related miRNAs were screened by TargetScan, miRWalk, and Gene Expression Omnibus. The expressions of P2Y12 and miRNAs in the HPR group and the LPR group were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pearson correlation analysis was used to determine the correlation between P2Y12 and miRNAs. The interactions between P2Y12 and miR-107 were predicted by TargetScan and verified by dual-luciferase reporter assay. The regulation of miR-107 mimic or inhibitor on P2Y12 expression was detected by qRT-PCR and Western blot. Results: There were 22 patients in the LPR group and 28 patients in the HPR group. PY212 was highly expressed in the HPR group compared with the LPR group. We screened the P2Y12-related miRNAs (miR-145-5p, miR-4701-3p, miR-107, and miR-15b-5p), but only miR-107 and miR-15b-5p expressions were downregulated in the HPR group and were negatively correlated with PY212 expression. P2Y12 was the target gene of miR-107. PY212 expression was inhibited by miR-107 overexpression but suppressed by miR-107 silencing. Conclusion: Platelet miR-107 participated in clopidogrel resistance in ACS/PCI patients by regulating P2Y12 expression.