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

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs) like miR-145-5p and miR-133a-3p are implicated in inflammation, oxidative stress, and vascular integrity, processes crucial to sickle cell disease (SCD) pathophysiology.
• Understanding miRNA expression in SCD can offer insights into disease mechanisms and potential therapeutic targets.

Purpose of the Study:

• To investigate the expression levels of miR-145-5p and miR-133a-3p in pediatric SCD patients during vaso-occlusive crisis (VOC) and steady-state conditions.
• To evaluate the potential of these miRNAs as clinical biomarkers for SCD activity and vaso-occlusive complications.

Main Methods:

• A case-control study involving 45 pediatric SCD patients (24 VOC, 21 steady-state) and 45 healthy controls.
• Quantification of plasma miR-145-5p and miR-133a-3p using real-time quantitative PCR.
• Correlation analysis with clinical characteristics, laboratory parameters, genotype, and hydroxyurea (HU) therapy; Receiver Operating Characteristic (ROC) analysis for diagnostic accuracy.

Main Results:

• Circulating miR-133a-3p and miR-145-5p levels were significantly higher in SCD patients compared to controls (p < 0.001), with further elevation during VOC (p < 0.050).
• miR-133a-3p levels correlated with fetal hemoglobin (HbF), reticulocyte count, and urine albumin/creatinine ratio (p < 0.050).
• Both miRNAs demonstrated reasonable diagnostic accuracy in distinguishing VOC from steady-state (AUC = 0.69).

Conclusions:

• miR-133a-3p and miR-145-5p show promise as biomarkers for assessing SCD activity.
• The association of miR-133a-3p with HbF and urine albumin/creatinine ratio suggests clinical relevance in vaso-occlusive complications.
• Further longitudinal and functional studies are warranted to validate these findings and explore therapeutic potential.