Unveiling molecular mechanisms and therapeutic targets in HbH-CS disease: a focus on oxidative stress and mitochondrial dysfunction

This study aimed to investigate the molecular mechanisms and therapeutic targets related to oxidative stress and mitochondrial dysfunction in Hemoglobin H-Constant Spring (HbH-CS) disease. HbH-CS differentially expressed genes (DEGs) were selected from a microarray dataset. Oxidative stress-related genes (OSGs) and mitochondrial function-related genes (MiRGs) were retrieved from public databases. Oxidative stress and mitochondrial function-related genes (OMRGs) were defined as the intersection of HbH-CS DEGs, OSGs, and MiRGs. Programmed cell death (PCD) mechanisms and functional enrichment analyses were subsequently investigated. A protein–protein interaction (PPI) network was constructed to identify hub genes, and potential regulatory mechanisms and expression levels of candidate genes were further explored. A total of 98 OMRGs were identified, which were associated with cellular respiration, oxidative stress response, mitochondrial membrane, and apoptotic signaling. Apoptosis was determined to be the primary PCD mechanism. Three hub genes were identified: AKT serine/threonine kinase 1 (AKT1), B cell lymphoma/leukemia-2 (BCL2), and cytochrome c , somatic (CYCS). Additionally, RNA-binding motif protein 15B (RBM15B) was recognized as a shared N6-methyladenosine (m 6 A) regulator. The mRNA expression levels of these four genes were significantly downregulated in HbH-CS patients. These findings provide novel insights into the molecular mechanisms and identify potential therapeutic targets for clinical intervention.