Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Int J Lab Hematol. 2020 Oct;42(5):501-509. doi: 10.1111/ijlh.13245. Epub 2020 Jun 3.
MicroRNAs (miRNAs) play a critical role in orchestrating T cell differentiation and activation and may thus play a vital role in acquired aplastic anemia (aAA). The study aimed to evaluate the differential expression of selected miRNAs and their relevant target genes in bone marrow samples of aAA patients.
Differential expression of 8 miRNAs viz; hsa-miR-126-3p, miR-145-5p, miR-155-5p, miR-150-5p, miR-146b-5p, miR-34a, miR-29a, and miR-29b was evaluated in the bone marrow mononuclear cells of aAA patients. TaqMan microRNA assay was performed for preparing the cDNA of specific miRNA, followed by expression analysis using qRT-PCR. Data were normalized using two endogenous controls, RNU6B and RNU48. Delta-delta CT method was used to calculate the fold change (FC) of miRNA expression in individual samples, and a FC of >1.5 was taken as significant. Target genes of these miRNAs were evaluated by qRT-PCR.
Thirty five samples of aAA patients and 20 controls were evaluated. Irrespective of the disease severity, five miRNAs were found to be deregulated; miR-126 (FC-0.348; P-value-.0001) and miR-145 (FC-0.31; P-value-.0001) were downregulated, while miR-155 (FC-3.50; P-value-.0067), miR-146 (FC-3.13; P-value-.0105), and miR-150 (FC-5.78; P-value-.0001) were upregulated. Target gene study revealed an upregulation of PIK3R2, MYC, SOCS1, and TRAF-6, and downregulation of MYB.
This is the first study from the Indian subcontinent demonstrating the presence of altered miRNA expression in the bone marrow samples of aAA patients, suggesting their role in the pathogenesis of the disease. A comprehensive study focusing on the effect of these miRNA-mRNA interactions is likely to open new avenues of management.
微小 RNA（miRNA）在协调 T 细胞分化和激活方面发挥着关键作用，因此可能在获得性再生障碍性贫血（aAA）中发挥重要作用。本研究旨在评估骨髓样本中选定 miRNA 及其相关靶基因在 aAA 患者中的差异表达。
评估 8 种 miRNA 的差异表达，即 hsa-miR-126-3p、miR-145-5p、miR-155-5p、miR-150-5p、miR-146b-5p、miR-34a、miR-29a 和 miR-29b，在 aAA 患者的骨髓单核细胞中。采用 TaqMan 微小 RNA 检测法制备特定 miRNA 的 cDNA，然后使用 qRT-PCR 进行表达分析。数据使用两个内参 RNU6B 和 RNU48 进行归一化。采用 Delta-delta CT 方法计算个体样本中 miRNA 表达的倍数变化（FC），FC>1.5 被认为具有显著性。通过 qRT-PCR 评估这些 miRNA 的靶基因。
评估了 35 例 aAA 患者和 20 例对照。无论疾病严重程度如何，有 5 种 miRNA 被发现失调；miR-126（FC-0.348；P 值-.0001）和 miR-145（FC-0.31；P 值-.0001）下调，而 miR-155（FC-3.50；P 值-.0067）、miR-146（FC-3.13；P 值-.0105）和 miR-150（FC-5.78；P 值-.0001）上调。靶基因研究显示 PIK3R2、MYC、SOCS1 和 TRAF-6 上调，而 MYB 下调。
这是来自印度次大陆的第一项研究，证明了 aAA 患者骨髓样本中存在 miRNA 表达改变，表明它们在疾病发病机制中的作用。一项专注于这些 miRNA-mRNA 相互作用影响的综合研究可能会开辟新的管理途径。
