miR-30a-5p induces the adipogenic differentiation of bone marrow mesenchymal stem cells by targeting FAM13A/Wnt/β-catenin signaling in aplastic anemia

Abstract

Aplastic anemia (AA) is a bone marrow failure syndrome with high morbidity and mortality. Bone marrow (BM)-mesenchymal stem cells (MSCs) are the main compo- nents of the BM microenvironment, and dysregulation of BM-MSC adipogenic differentiation is a pathologic hallmark of AA. MicroRNAs (miRNAs/miRs) are crucial regulators of multiple pathological processes such as AA. However, the role of miR-30a-5p in the modulation of BM-MSC adipogenic differentiation in AA remains unclear. The present study aimed to explore the effect of miR-30a-5p on AA BM-MSC adipogenic differentiation and the underlying mechanism. The levels of miR-30a-5p expression and family with sequence similarity 13, member A (FAM13A) mRNA expression in BM-MSCs were quantified using reverse transcription-quantitative (RT-q) PCR. The mRNA expression levels of adipogenesis-associated factors [fatty acid-binding protein 4 (FABP4), lipoprotein lipase (LPL), perilipin-1 (PLIN1), peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)] were analyzed using RT-qPCR. Lipid droplet accumulation was evaluated using Oil Red O staining in BM-MSCs. The interaction between miR-30a-5p and the FAM13A 3'-untrans- lated region was identified by TargetScan, and a dual-luciferase reporter assay was used to confirm the interaction. The expres- sion levels of FAM13A and Wnt/β-catenin pathway-related proteins were examined via western blotting. The results showed that miR-30a-5p expression levels were significantly elevated in BM-MSCs from patients with AA compared with those in control subjects (iron deficiency anemia). miR-30a-5p expres- sion levels were also significantly increased in adipose-induced BM-MSCs in a time-dependent manner. miR-30a-5p signifi- cantly promoted AA BM-MSC adipogenic differentiation, and significantly enhanced the mRNA expression levels of FABP4, LPL, PLIN1, PPARγ and C/EBPα as well as lipid droplet accumulation. miR-30a-5p was also demonstrated to target FAM13A in AA BM-MSCs. FAM13A significantly reduced BM-MSC adipogenic differentiation by activating the Wnt/β-catenin signaling pathway. In conclusion, miR-30a-5p was demonstrated to serve a role in AA BM-MSC adipogenic differentiation by targeting the FAM13A/Wnt/β-catenin signaling pathway. These findings suggest that miR-30a-5p may be a therapeutic target for AA.