MicroRNA let-7f-5p regulates neuronal differentiation of rat bone marrow mesenchymal stem cells by targeting Par6α

Highlights: • A neuronal differentiation mechanism for bone marrow MSCs is proposed. • Let-7f-5p is downregulated and Par6α is upregulated in neuron-like cells differentiated from MSCs. • Par6α is a target gene of let-7f-5p. • Let-7f-5p inhibits the neurogenic differentiation of MSCs. • Downregulation of let-7f-5p promotes the neuronal polarity during MSCs differentiation by upregulating Par6α. Par6α (partitioning defective 6 homologue alpha), a component of the Par3/Par6/aPKC complex, was recently shown to be essential for axon specification during neuronal development. However, the biological functions and regulatory mechanisms of Par6α in the mesenchymal stem cell (MSC) differentiation process have not been investigated. In this study, we found that the expression of let-7f-5p was downregulated during differentiation of bone marrow-derived MSCs to neuron-like cells. Interestingly, Par6α was predicted to be a target gene of let-7f-5p by computerized analysis and the luciferase reporter assay. Using gain- and loss-of-function approaches, we found that expression of Par6α was inversely correlated with let-7f-5p levels during differentiation (p < 0.05). By silencing Par6α using siRNAs, we demonstrated that Par6α was necessary for MSC neuronal differentiation. Altogether, our studies proved that inhibition of let-7f-5p facilitates induction of MSCs into neuron-like cells by directly targeting Par6α.