MicroRNA-126 promotes proliferation, migration, invasion and endothelial differentiation while inhibits apoptosis and osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used for the treatment of inflammatory and immune diseases, and microRNA-126 (miR-126) is a critical regulator in inflammation as well as immunity. However, the mediating role of miR-126 in BMSCs is still not clear. Thus, this study aimed to preliminarily investigate the effect of miR-126 on proliferation, apoptosis, migration, invasion, differentiation, and its potential regulating pathways in BMSCs. Human BMSCs were obtained and infected with miR-126 overexpression lentivirus, control overexpression lentivirus, miR-126 knock-down lentivirus and control knock-down lentivirus, then cell functions, the PI3 K/AKT pathway and MEK1/ERK1 pathway were evaluated. Subsequently, PI3 K overexpression plasmid and MEK1 overexpression plasmid were transfected into BMSCs with miR-126 knockdown, then the cell functions were assessed as well. BMSCs with miR-126 overexpression displayed elevated proliferation, migration and invasion while decreased apoptosis; however, BMSCs with miR-126 knockdown presented with decreased proliferation, migration, invasion but increased apoptosis. As for differentiation, BMSCs with miR-126 overexpression showed higher levels of CD31, eNOS and VE-cadherin but lower expressions of ALP, OPN and RUNX2, while BMSCs with miR-126 knockdown disclosed the opposite results. Additionally, BMSCs with miR-126 overexpression showed elevated PI3 K, pAKT, MEK1 and pERK1 expressions, while BMSCs with miR-126 knockdown displayed opposite results. Furthermore, PI3 K overexpression and MEK1 overexpression both reversed the effects of miR-126 on cell functions in BMSCs. In conclusion, miR-126 is a genetic regulator in BMSCs via modulating multiple cell functions through the PI3 K/ AKT and MEK1/ERK1 signaling pathways.

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose-derived stem cells from diabetic, old, and young patients

“…Our results revealed that eight miRNAs were differentially expressed between Y-ASCs and O-ASCs. Of these eight miRNAs, miR-210-3p [ 58 ] and miR-126 [ 59 ] could inhibit apoptosis in ASCs and BMMSCs, while miR-214-3p could anticipate in the therapeutic application of mesenchymal stem cell-derived extracellular vesicles for attenuating radiation-induced lung injury [ 60 ]. However, all three miRNAs were downregulated in O-ASCs, which might have contributed to their poor function.…”

The whole profiling and competing endogenous RNA network analyses of noncoding RNAs in adipose stem cells from diabetic, old and young patients

“…Our results revealed eight miRNAs (miR-145-3P, miR-145-5p, miR-126-3p, miR-126-5p, miR-214-3p, miR-181a-3p, miR-210-3p, miR-766-3p) were differentially expressed between Y-ASCs and O-ASCs. Of them, miR-210-3p [52] and miR-126 [53] could inhibit the apoptosis of ASCs and BMMSCs, miR-214-3p could anticipate in the therapeutic function of MSCs derived extracellular vesicles for attenuating radiation-induced lung injury [54]. However, all these three miRNAs were down-regulated in O-ASCs, which might be part of the reasons for their poor function.…”

Preclinical Evaluation of Bone Marrow Mesenchymal Stem Cells Overexpressing MicroRNA-126 to Treat Critical Limb Ischemia

“…Two important targets of miR-126 including PIK3R2 (P85β) and SPRED1 play an important role as an inhibitor of PI3K (in PI3K/AKT signaling pathway) and RAF1 (in MAPK/ERK1 signaling pathway) respectively [32,33]. In BM-MSCs miR−126 , miR-126 targets these two negative regulators of pathways and leading to promote signaling pathways that results in MSCs proliferation and increase paracrine secretion [34,35].…”