<p>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 <i>GATA2</i>‑associated ceRNA network, emphasizing the <i>hsa_circ_0005245</i>_<i>hsa-miR-425-3p</i>_<i>GATA2</i> pathway. Validation using qRT-PCR analysis in β-TM samples, RNA immunoprecipitation, and dual-luciferase reporter assays confirmed this pathway. Furthermore, overexpression of <i>hsa_circ_0005245</i>, <i>hsa-miR-425-3p</i>, and <i>GATA2</i> in HUDEP-2 cells individually resulted in elevated γ-globin levels. Our findings identify a novel <i>hsa_circ_0005245</i>_<i>hsa-miR-425-3p</i>_<i>GATA2</i> pathway that regulates γ-globin expression, providing potential insights for the clinical management of β-TM patients.</p>

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

  • Tao Wu,
  • Zhenmin Ren,
  • Xiaorong Liu,
  • Zhihao Xing,
  • Xiaoying Fu,
  • Wujiao Li,
  • Moxian Chen,
  • Defa Li,
  • Yunsheng Chen

摘要

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.