Systematic identification and validation of ceRNA-driven regulatory mechanisms in pediatric β-Thalassemia major

作者：Tao Wu, Zhen-Min Ren, Xiaorong Liu, Zhihao Xing, Xiaoying Fu, Wujiao Li, Mo‐Xian Chen, Defa Li, Yunsheng Chen · 发表于：Annals of Hematology · 年份：2025 · DOI：10.1007/s00277-025-06215-2 · 被引用次数：3 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、Cancer-related molecular mechanisms research

Reactivation of fetal hemoglobin (Hb F, α2γ2) has been demonstrated to be a therapeutic strategy for patients with β-hemoglobinopathies. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by silencing RNA. Both coding and non-coding RNAs can compete for the same miRNAs, acting as competing endogenous RNAs (ceRNAs). However, the role of ceRNAs in β-thalassemia major (β-TM) and their impact on γ-globin expression remains poorly understood. In this study, we conducted transcriptome sequencing to collect circularRNA (circRNA), miRNA, and mRNAs from β-TM patients and healthy individuals. Through bioinformatics analysis, we constructed a GATA2‑associated ceRNA network, emphasizing the hsa_circ_0005245_hsa-miR-425-3p_GATA2 pathway. Validation using qRT-PCR analysis in β-TM samples, RNA immunoprecipitation, and dual-luciferase reporter assays confirmed this pathway. Furthermore, overexpression of hsa_circ_0005245, hsa-miR-425-3p, and GATA2 in HUDEP-2 cells individually resulted in elevated γ-globin levels. Our findings identify a novel hsa_circ_0005245_hsa-miR-425-3p_GATA2 pathway that regulates γ-globin expression, providing potential insights for the clinical management of β-TM patients.