miR­30a­5p induces the adipogenic differentiation of bone marrow mesenchymal stem cells by targeting FAM13A/Wnt/ß­catenin signaling in aplastic anemia.

Aplastic anemia (AA) is a bone marrow failure syndrome with high morbidity and mortality. Bone marrow (BM)­mesenchymal stem cells (MSCs) are the main components of the BM microenvironment, and dysregulation of BM­MSC 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 miR­30a­5p in the modulation of BM­MSC adipogenic differentiation in AA remains unclear. The present study aimed to explore the effect of miR­30a­5p on AA BM­MSC adipogenic differentiation and the underlying mechanism. The levels of miR­30a­5p expression and family with sequence similarity 13, member A (FAM13A) mRNA expression in BM­MSCs were quantified using reverse transcription­quantitative (RT­q) PCR. The mRNA expression levels of adipogenesis­associated factors [fatty acid­binding protein 4 (FABP4), lipoprotein lipase (LPL), perilipin­1 (PLIN1), peroxisome proliferator­activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)] were analyzed using RT­qPCR. Lipid droplet accumulation was evaluated using Oil Red O staining in BM­MSCs. The interaction between miR­30a­5p and the FAM13A 3'­untranslated region was identified by TargetScan, and a dual­luciferase reporter assay was used to confirm the interaction. The expression levels of FAM13A and Wnt/ß­catenin pathway­related proteins were examined via western blotting. The results showed that miR­30a­5p expression levels were significantly elevated in BM­MSCs from patients with AA compared with those in control subjects (iron deficiency anemia). miR­30a­5p expression levels were also significantly increased in adipose­induced BM­MSCs in a time­dependent manner. miR­30a­5p significantly promoted AA BM­MSC adipogenic differentiation, and significantly enhanced the mRNA expression levels of FABP4, LPL, PLIN1, PPARγ and C/EBPα as well as lipid droplet accumulation. miR­30a­5p was also demonstrated to target FAM13A in AA BM­MSCs. FAM13A significantly reduced BM­MSC adipogenic differentiation by activating the Wnt/ß­catenin signaling pathway. In conclusion, miR­30a­5p was demonstrated to serve a role in AA BM­MSC adipogenic differentiation by targeting the FAM13A/Wnt/ß­catenin signaling pathway. These findings suggest that miR­30a­5p may be a therapeutic target for AA.