Circulating miR-145-5p and miR-133a-3p in pediatric sickle cell disease: biomarker potential for vaso-occlusive crises and disease activity

MicroRNAs (miRNAs) involving miR-145-5p and miR-133a-3p are increasingly recognized for their roles in modulating inflammation, oxidative stress, and vascular integrity, key processes implicated in sickle cell disease (SCD) pathophysiology. To investigate the expression levels of miR-145-5p and miR-133a-3p in pediatric SCD patients during vaso-occlusive crisis (VOC) as well as steady-state conditions, and to evaluate their potential as clinical biomarkers. A case-control study was conducted including 45 pediatric SCD patients (24 during VOC and 21 in steady-state) and 45 age- and sex-matched healthy controls. Plasma miR-145-5p and miR-133a-3p levels were quantified using real-time quantitative PCR and correlated with clinical characteristics, laboratory parameters, genotype, and hydroxyurea (HU) therapy. Circulating miR-133a-3p and miR-145-5p were significantly higher in SCD patients than in controls (p < 0.001), with a further elevation during VOC compared to steady-state (p < 0.050). While no significant association was found with genotype or HU therapy (p > 0.05), miR-133a-3p levels correlated significantly with fetal hemoglobin (HbF) (p = 0.006), reticulocyte count (p = 0.049), and urine albumin/creatinine ratio (p = 0.043). A strong positive correlation was observed between both miRNAs (r = 0.683, p < 0.001). Receiver Operating Characteristic (ROC) analysis demonstrated reasonable diagnostic accuracy of both miRNAs in distinguishing VOC from steady-state (AUC = 0.69). This study highlights the potential of miR-133a-3p and miR-145-5p as biomarkers for SCD activity. The association of miR-133a-3p with HbF and urine A/C ratio further suggests clinical relevance in vaso-occlusive complications. Larger longitudinal and functional studies are needed to validate these findings.