Expression of miR-145 and Its Target Proteins Are Regulated by miR-29b in Differentiated Neurons

Abstract

MicroRNAs (miRNAs) are emerging as the most potential regulator of neuronal development. Recent studies from our lab and elsewhere have demonstrated a direct role of miRNAs in regulating neuronal differentiation and synaptogenesis. MicroRNA-145, a miRNA identified to regulate pluripotency of stem cells, downregulates the protein levels of reprogramming transcription factors (RTFs) like OCT4, SOX2, and KLF4 (cell, 137,647–658,2009). Studies have shown that miR-145 is multifunctional and crucial for fate determination of neurons. In our recently published study, we have identified a set of miRNAs including miR-145 and miR-29b families differentially expressed in SH-SY5Y cells exposed sequentially with retinoic acid + brain-derived neurotrophic factor (RA+BDNF) for differentiation into mature neurons (Mol Neurobiol (2016) doi:https://doi.org/10.1007/s12035-016-0042-9). In the present study, we have identified the role of miR-29b in upregulation of miR-145, which is upregulated after exposure of RA+BDNF in a P53-dependent manner. In differentiating SH-SY5Y cells, expression of miR-29b downregulates expression of P85α, a P53 inhibitor, which results in upregulation of miR-145 and downregulation of RTF proteins. Ectopic expression of miR-145 and miR-29b in amounts equivalent to their endogenous expression has induced G1 phase cell cycle arrest. In conclusion, our studies have identified miR-29b as an upstream regulator of miR-145 and targets its RTF genes during differentiation of SH-SY5Y cells.