Serum miR-221-3p as a new potential biomarker for depressed mood in perioperative patients

Abstract

MicroRNAs (miRNAs) modulate various genes associated with brain disorders and circulating miRNAs may therefore serve as biomarkers for these neurological diseases. We previously found that the miRNA miR-221-3p was highly expressed in cerebrospinal fluid and the serum of major depressive disorder (MDD) patients. Here, we examined whether miR-221-3p could be used as a biomarker for depressed mood in perioperative patients. We first examined the relative expression of serum miR-221-3p by real-time quantitative PCR in perioperative patients with different degrees of depressive mood assessed by the Patient Health Questionnaire-9 (PHQ-9) diagnostic form. We found that miR-221-3p expression in the mild depressive mood group (PHQ-9 scores 5-9) was 2.21 fold that of the normal group (PHQ-9 scores 0-4) and the moderate＆severe depressive mood group (PHQ-9 scores ≥ 10) showed miR-221-3p expression levels 3.66 fold that of the normal group. Then the absolute quantification of serum miR-221-3p was obtained using an miRNA standard curve. We found that the amount of serum miR-221-3p was positively correlated with depressed mood; when serum miR-221-3p > 1.7×107 copies/μg RNA, all indicated PHQ-9 scores were higher than 6. Subsequently, we found that miR-221-3p could indirectly increase the expression of IFN-α (Interferon alpha) in astrocytes by targeting IRF2 (Interferon Regulatory Factor 2) and that miR-221-3p participated in the anti-neuroinflammatory signaling cascades induced by ketamine and paroxetine via the IRF2/IFN-α pathway. Our results indicate that elevated serum miR-221-3p can be used as a biomarker for depressed mood in perioperative patients and that IFN-α-induced NF-κB activation in astrocytes mediated by miR-221-3p targeting of IRF2 may be one of the potential mechanisms.