Differential expression of miRNAs and their target genes: Exploring a new perspective of acquired aplastic anemia pathogenesis

Abstract

Introduction 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. Methods 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. Results 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. Conclusion 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.

Mechanism of human chorionic gonadotropin in endometrial receptivity via the miR‐126‐3p/PI3K/Akt/eNOS axis

“…al showed significantly upregulated miR‐122 in the ovary after hCG treatment 37 . Likewise, consistent with the previous research, 38 our results noted that miR‐126‐3p targeted PIK3R2 and PIK3R2 level was raised after miR‐126‐3p inhibition. Moreover, in vitro studies unveiled that EEC proliferation was enhanced upon hCG treatment but weakened after miR‐126‐3p inhibition.…”

“…hCG is classically acknowledged for its role in stimulating trophoblast invasion and functional differentiation. 38 Compelling evidence supports that miR-126 promotes endothelial cell proliferation, migration, survival, and angiogenesis via downregulating PIK3R2 and is related to MVD increase and Akt activation in the placenta. 35 Our findings first revealed the regulation of hCG on miR-126-3p and PIK3R2 in EID mice.…”

“…Moreover, in vitro studies unveiled that EEC proliferation was enhanced upon hCG treatment but weakened after miR‐126‐3p inhibition. hCG is classically acknowledged for its role in stimulating trophoblast invasion and functional differentiation 38 . Compelling evidence supports that miR‐126 promotes endothelial cell proliferation, migration, survival, and angiogenesis via downregulating PIK3R2 and is related to MVD increase and Akt activation in the placenta 35 .…”

Hypoplastic myelodysplastic syndrome and acquired aplastic anemia: Immune‑mediated bone marrow failure syndromes (Review)

“…Compared with hMDS, acquired AA has more available miRNA data (Table II). Srivastava et al (51) recently found deregulated expression of miR-126, miR-145, miR-155, miR-146 and miR-150 in AA, and determined their target genes, phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2), MYC proto-oncogene (MYC), suppressor of cytokine signaling 1, TRAF6 and MYB proto-oncogene, respectively. In other recent study, Lu et al (52) integrated multiple expression profiles of miRNAs and mRNAs of BM T cells from patients with acquired AA and showed that miR-34a-5p, miR-195-5p and miR-424-5p may modulate T-cell differentiation and plasticity by targeting histone gene expression and histone modification.…”

The impact of clonal hematopoiesis on outcomes in patients with aplastic anemia

“…MicroRNAs (miRNAs) can regulate T cell differentiation and plasticity by targeting their corresponding message RNAs (mRNAs), which play important roles in many autoimmune diseases and also AA [70][71][72][73].…”