Fakhr-Eldeen Abeer, Toraih Eman A, Fawzy Manal S
a Department of Clinical Pathology, Faculty of Medicine , Sohag University , Sohag , Egypt.
b Department of Pathology, Faculty of Medicine , Northern Border University , Arar , Saudi Arabia.
Hematology. 2019 Dec;24(1):308-317. doi: 10.1080/16078454.2019.1570616.
Beta-thalassemia (β-thal) is one of the most common genetic disorders worldwide. Multiple genetic and epigenetic mechanisms could be implicated in the pathogenesis and/or phenotype variations. We sought to explore the serum expression profile of three disease-related long non-coding RNAs (lncRNAs) in a sample of Egyptian β-thal patients with correlation to the patients' clinicolaboratory data.
Fifty consecutive β-thal patients and 50 unrelated controls were enrolled in the study. Quantification of circulating lncRNAs; MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), MIAT (myocardial infarction associated transcript), and ANRIL (antisense non-coding RNA in the INK4 locus) was done by Real-time qRT-PCR.
Significant higher expression levels of the studied lncRNAs in β-thal patients compared to the controls (all P values < 0.001) were identified. There was no significant difference between β-thal-major and intermedia patients at the level of any of the studied lncRNAs. Higher MALAT1 expression profile was associated with early age at onset, early age at first blood transfusion, and a higher frequency of splenomegaly. Whereas, up-regulated MIAT levels were associated with early age at first blood transfusion.
Taken together, the studied lncRNAs MALAT1, MIAT, and ANRIL might be implicated in β-thal pathogenesis and could provide new molecular biomarkers for β-thalassemia after validation in large-scale future studies.
β地中海贫血(β-地贫)是全球最常见的遗传性疾病之一。多种遗传和表观遗传机制可能与发病机制和/或表型变异有关。我们试图探讨埃及β-地贫患者样本中三种疾病相关长链非编码RNA(lncRNA)的血清表达谱,并将其与患者的临床实验室数据相关联。
本研究纳入了50例连续的β-地贫患者和50例无关对照。通过实时定量逆转录聚合酶链反应(Real-time qRT-PCR)对循环lncRNA进行定量分析,包括转移相关的肺腺癌转录本1(MALAT1)、心肌梗死相关转录本(MIAT)和INK4基因座中的反义非编码RNA(ANRIL)。
与对照组相比,β-地贫患者中所研究的lncRNA表达水平显著更高(所有P值均<0.001)。在任何所研究的lncRNA水平上,重型和中间型β-地贫患者之间均无显著差异。较高的MALAT1表达谱与发病年龄早、首次输血年龄早以及脾肿大频率较高相关。而MIAT水平上调与首次输血年龄早相关。
综上所述,所研究的lncRNA MALAT1、MIAT和ANRIL可能与β-地贫发病机制有关,并且在未来大规模研究验证后可能为β地中海贫血提供新的分子生物标志物。