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


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.


CONCLUSIONS
Our study therefore enhances the present understanding of the therapeutic potential of NSCs in CNS disorders.
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Juhyun
J
Song
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Yumi
Y
Oh
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.
Jong Youl
JY
Kim
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea.
Kyoung Joo
KJ
Cho
Department of Anatomy, Yonsei University College of Medicine, Seoul, Korea.|Brain Korea 21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea. jelee@yuhs.ac.
Jong Eun
JE
Lee
D000376:Agmatine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D035683:MicroRNAs; D000376:Agmatine
DCX; ERK; Neural stem cell (NSCs); TLX; agmatine; microRNA let-7a (let-7a)