Cellular Prion Protein Promotes Neuronal Differentiation of Adipose-Derived Stem Cells by Upregulating miRNA-124

The cellular prion protein (PrPC) is a highly conserved glycoprotein anchored by glycosylphosphatidylinositol (GPI) to the cell surface and is also the source of pathogenic agent of scrapie prion protein (PrPSc). Numerous researches have suggested putative physiological roles for PrPC, including protection from ischemic and excitotoxic lesions, and participation in cell signaling and differentiation. Here, we demonstrated that PrPC positively regulates neuronal differentiation of mouse adipose-derived stem cells (ADSCs). The small C-terminal domain phosphatase 1 (SCP1) expression was knocked down by gene silencing. The mRNA expression of miRNA-124 and PrPC was measured with quantitative PCR. Western blot analysis was used to detect the protein levels of nestin, beta III-tubulin, and SCP1, and dual-luciferase reporter assay was performed to test the target of miRNA-124. The expression level of PrPC was found to increase steadily during neuron-like differentiation process, and PrPC knockout resulted in the reduction of neuron-like cell markers. We further showed that miRNA-124 could directly target SCP1-3'-untranslated region to decrease small C-terminal domain phosphatase 1 (SCP1) SCP1, and that miRNA-124 expression is regulated by PrPC. Our results suggest that PrPC may play a key role in the neuronal differentiation of ADSC through modulating miRNA-124-SCP1 axis. To date, this is the first time strong evidence for the involvement of PrPC in the neuronal differentiation of ADSC is reported.