Suppression of MicroRNAlet-7aExpression by Agmatine Regulates Neural Stem Cell Differentiation

Abstract

PurposeNeural stem cells (NSCs) effectively reverse some severe central nervous system (CNS) disorders, due to their ability to differentiate into neurons. Agmatine, a biogenic amine, has cellular protective effects and contributes to cellular proliferation and differentiation in the CNS. Recent studies have elucidated the function of microRNA let-7a (let-7a) as a regulator of cell differentiation with roles in regulating genes associated with CNS neurogenesis.Materials and MethodsThis study aimed to investigate whether agmatine modulates the expression of crucial regulators of NSC differentiation including DCX, TLX, c-Myc, and ERK by controlling let-7a expression.ResultsOur data suggest that high levels of let-7a promoted the expression of TLX and c-Myc, as well as repressed DCX and ERK expression. In addition, agmatine attenuated expression of TLX and increased expression of ERK by negatively regulating let-7a.ConclusionOur study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.

Identification of potential molecular pathogenesis mechanisms modulated by microRNAs in patients with Intestinal Neuronal Dysplasia type B

“…miRNA let-7a showed high expression (17-fold) in plasma from patients with IND-B, compared to healthy controls. miRNA let-7 belongs to a family of miRNAs present in multiple genomic locations, and consists of 9 members 42,43 . Genes such as cyclin A2 , CDC34 , Aurora A and B kinases ( STK6 and STK12 ), E2F5 , and CDK8 were characterized as responsive to changes in miRNA let-7a levels.…”

“…These genes are related to the regulation of the cell cycle, involving mechanisms of apoptosis and cellular proliferation 44 , which are biological processes that could explain the hyperplasia of nerve plexuses of the enteric nervous system that occurs in IND-B. Furthermore, miR let-7 suppresses the differentiation of human embryonic stem cell derived neural progenitor cells and influences self-renewal of neural stem cells 43,44 . Over-expression of let-7a influences neural stem cells proliferation and differentiation 43,45 .…”

“…Furthermore, miR let-7 suppresses the differentiation of human embryonic stem cell derived neural progenitor cells and influences self-renewal of neural stem cells 43,44 . Over-expression of let-7a influences neural stem cells proliferation and differentiation 43,45 . However, the mechanisms of this interaction have not been elucidated yet 43 .…”

MiRNA Influences in Neuroblast Modulation: An Introspective Analysis

“…Overexpression of let-7a directly affects both proliferation and differentiation of NSCs, though further elucidation is required to understand the mechanism of action [ 119 , 120 ]. Agmatine, an endogenous amine produced by decarboxylation of L-arginine by arginine decarboxylase [ 121 ], can enhance NSC differentiation into neurones by modulating expression of let-7a [ 122 ]. It also regulates neuroprotection and increases neuronal differentiation in NSCs by activating extracellular signal-regulated protein kinases 1 and 2 (ERK1/2)—members of the mitogen-activated protein kinase super family—and can mediate cell proliferation [ 123 ].…”

“…It also regulates neuroprotection and increases neuronal differentiation in NSCs by activating extracellular signal-regulated protein kinases 1 and 2 (ERK1/2)—members of the mitogen-activated protein kinase super family—and can mediate cell proliferation [ 123 ]. Agmatine promotes ERK activation by negatively regulating let-7a such that, if it is overexpressed, leads to decreased ERK phosphorylation [ 122 ].…”