MicroRNAs are important in the development, functioning, and pathophysiology of the central nervous system. Here, we show that increasing the levels of microRNA-320 (miR-320) for 3 days markedly increases neurite length, and at 4 days, reduces the total cell number in Neuro-2A cells. In-silico analysis of possible miR-320 targets identified cAMP-regulated phosphoprotein-19 kDa (ARPP-19) and semaphorin 3a as potential targets that could be involved. ARPP-19 was validated by showing reduced mRNA and protein levels when miR-320 was overexpressed, whereas miR-320 had no effect on semaphorin 3a expression. ARPP-19 is known to inhibit protein phosphatase-2A activity, which inhibits mitosis and induces neurite outgrowth, making this the likely mechanism. Thus, increased levels of miR-320 lead to decreased levels of ARPP-19, increased neurite length, and fewer total cells. These data suggest that miR-320 could play a role in neuronal development and might be a target to enhance neuronal regeneration following injury.
Department of Anesthesia, Stanford University School of Medicine, California, USA
Correspondence to Rona G. Giffard, MD, PhD, Department of Anesthesia, Stanford University School of Medicine, Stanford University, 300 Pasteur Drive, Grant Building, S272A, Stanford, CA 94305-5117, USA Tel: +1 650 725 8482; fax: +1 650 725 8052; e-mail: firstname.lastname@example.org
Received March 15, 2012
accepted March 22, 2012