hsa-miR-190b-5p 在小儿β-地中海贫血患者外周血中的临床价值及其对 BCL11A 表达的调控。
The clinical value of hsa-miR-190b-5p in peripheral blood of pediatric β-thalassemia and its regulation on BCL11A expression.
机构信息
Medical Genetic Diagnosis and Therapy Center of Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fujian Provincial Key Laboratory of Prenatal Diagnosis and Birth Defect, Fuzhou, Fujian Province, China.
Medical Research Center, Fujian Maternity and Child Health Hospital College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, China.
出版信息
PLoS One. 2023 Oct 5;18(10):e0292031. doi: 10.1371/journal.pone.0292031. eCollection 2023.
BACKGROUND
The B cell CLL/lymphoma 11A (BCL11A) is a key regulator of hemoglobin switching in β-thalassemia (β-thal). Previous study has suggested that dysregulated microRNAs are involved in the regulation of BCL11A expression. The aim of this study was to investigate the clinical value of hsa-miR-190b-5p in β-thal, and to confirm the regulatory effect of hsa-miR-190b-5p on BCL11A expression.
METHODS
The peripheral blood of 25 pediatric β-thal patients and 25 healthy controls were selected, and qRT-PCR was used to analyze the levels of hsa-miR-190b-5p and BCL11A mRNA. The relationship between hsa-miR-190b-5p expression and hematological parameters was assessed by Pearson's correlation test. The diagnostic power of hsa-miR-190b-5p was evaluated by ROC curves analysis. The direct integration between hsa-miR-190b-5p and BCL11A 3'-UTR was confirmed by luciferase reporter assay.
RESULTS
Hsa-miR-190b-5p expression in pediatric β-thal was upregulated, and negatively correlated with the MCH and HbA levels, but positively correlated with the HbF level. Hsa-miR-190b-5p showed a good diagnostic capability for pediatric β-thal equivalent to that of HbA2 (AUC: 0.760 vs. 0.758). Moreover, the levels of BCL11A mRNA in pediatric β-thal were decreased, and hsa-miR-190b-5p had a negative correlation with BCL11A mRNA expression (r = -0.403). BCL11A was a target gene of hsa-miR-190b-5p. The mRNA and protein levels of BCL11A were diminished by introduction of hsa-miR-190b-5p, whereas its expression was upregulated by knockdown of hsa-miR-190b-5p.
CONCLUSIONS
Hsa-miR-190b-5p expression was upregulated in pediatric β-thal and might be an effective diagnostic biomarker. BCL11A was negatively regulated by hsa-miR-190b-5p, which might provide new target for the treatment of pediatric β-thal.
背景
B 细胞 CLL/淋巴瘤 11A（BCL11A）是β-地中海贫血（β-thal）中血红蛋白开关的关键调节因子。先前的研究表明，失调的 microRNAs 参与了 BCL11A 表达的调节。本研究旨在探讨 hsa-miR-190b-5p 在 β-thal 中的临床价值，并证实 hsa-miR-190b-5p 对 BCL11A 表达的调节作用。
方法
选择 25 例儿科β-thal 患者和 25 例健康对照者的外周血，采用 qRT-PCR 分析 hsa-miR-190b-5p 和 BCL11A mRNA 的水平。采用 Pearson 相关检验评估 hsa-miR-190b-5p 表达与血液学参数之间的关系。通过 ROC 曲线分析评估 hsa-miR-190b-5p 的诊断能力。通过荧光素酶报告基因实验证实 hsa-miR-190b-5p 与 BCL11A 3'-UTR 的直接整合。
结果
儿科β-thal 中 hsa-miR-190b-5p 的表达上调，并与 MCH 和 HbA 水平呈负相关，与 HbF 水平呈正相关。hsa-miR-190b-5p 对儿科β-thal 的诊断能力与 HbA2 相当（AUC：0.760 与 0.758）。此外，儿科β-thal 中 BCL11A mRNA 的水平降低，hsa-miR-190b-5p 与 BCL11A mRNA 表达呈负相关（r=-0.403）。BCL11A 是 hsa-miR-190b-5p 的靶基因。引入 hsa-miR-190b-5p 可降低 BCL11A 的 mRNA 和蛋白水平，而敲低 hsa-miR-190b-5p 可上调其表达。
结论
hsa-miR-190b-5p 在儿科β-thal 中表达上调，可能是一种有效的诊断生物标志物。BCL11A 受 hsa-miR-190b-5p 的负调控，为儿科β-thal 的治疗提供了新的靶点。
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