Abstract
MicroRNA (miR)-128-3p is a brain-enriched miRNA that participates in the regulation of neural cell differentiation and the protection of neurons, but the mechanisms by which miR-128-3p regulates its target and downstream genes to influence cell fate from adult stem cells are poorly understood. In this study, we show down-regulation of miR-128-3p during all-trans retinoic acid (ATRA)-induced neurogenic differentiation from amniotic epithelial cells (AECs). We investigated miR-128-3p in both the Notch pathway and in the expression of neuron-specific genes predicted to be involved in miR-128-3p signaling to elucidate its role in the genetic regulation of downstream neurogenic differentiation. Our results demonstrate that miR-128-3p is a negative regulator for the transcription of the neuron-specific genes β III-tubulin, neuron-specific enolase (NSE), and polysialic acid-neural cell adhesion molecule (PSA-NCAM) via targeting Jagged 1 to inhibit activation of the Notch signaling pathway. We also used bioinformatics algorithms to screen for miR-128-3p interactions with long non-coding (lnc) RNA and circular RNA as competing endogenous RNAs to further elucidate underlying down-regulated molecular mechanisms. The lncRNA maternally expressed 3 is up-regulated by the ATRA/cAMP/CREB pathway, and it, in turn, is directly down-regulated by miR-128-3p to increase the amount of neuron differentiation. Endogenous miRNAs are, therefore, involved in neurogenic differentiation from AECs and should be considered during the development of effective cell transplant therapies for the treatment of neurodegenerative disease.
Highlights
MATERIALS AND METHODSAmniotic epithelial cells (AECs) are derived from the epiblast of the amniotic membrane and exhibit biological characteristics similar to embryonic stem cells, which have the capacity for differentiation into all three germ layers, as well as neural cells
The role of miRNAs in the differentiation and development of the nervous system has received increased attention and importance in recent research, and specific miRNA spatiotemporal expression patterns may be essential for neuron neurogenesis (Volvert et al, 2012; Zhang et al, 2014; Bai et al, 2019). miR-128 is a brain-enriched miRNA that was reported to participate in the regulation of neural cell differentiation
We showed that as the concentration of intracellular cAMP accumulates, and nuclear CREB concentrations increase after all-trans retinoic acid (ATRA) treatment in amniotic epithelial cells (AECs)
Summary
MATERIALS AND METHODSAmniotic epithelial cells (AECs) are derived from the epiblast of the amniotic membrane and exhibit biological characteristics similar to embryonic stem cells, which have the capacity for differentiation into all three germ layers, as well as neural cells. All-trans retinoic acid (ATRA) is the active ingredient of Vitamin A and plays an important role in the development of the nervous system by providing trophic effects that support the proliferation, differentiation, and maintenance of neural cells. The role of miRNAs in the differentiation and development of the nervous system has received increased attention and importance in recent research, and specific miRNA spatiotemporal expression patterns may be essential for neuron neurogenesis (Volvert et al, 2012; Zhang et al, 2014; Bai et al, 2019). Zhang et al (2016) demonstrated that miR-128 prevents cortical neural progenitor cells (NPCs) from dividing and supports the specialized development of cells in a mouse model. Removing miR-128 from mouse NPCs enhanced cell division, resulting in less neuron formation (Zhang et al, 2016)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
