Suppression of MicroRNA let-7a Expression by Agmatine Regulates Neural Stem Cell Differentiation

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Authors: Juhyun Song ; Yumi Oh ; Jong Youl Kim ; Kyoung Joo Cho ; Jong Eun Lee

MeSH: Agmatine/pharmacology* ; Cell Differentiation/drug effects* ; Cell Proliferation ; Humans ; MicroRNAs/metabolism* ; Neural Stem Cells/cytology ; Neural Stem Cells/drug effects* ; Neurogenesis/drug effects* ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism

Keywords: DCX ; ERK ; Neural stem cell (NSCs) ; TLX ; agmatine ; microRNA let-7a (let-7a)

Abstract: Purpose : Neural 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 Methods : This 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.

Results : Our 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.

Conclusion : Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.