4.3 Article

MicroRNA-320 induces neurite outgrowth by targeting ARPP-1

Journal

NEUROREPORT
Volume 23, Issue 10, Pages 590-595

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/WNR.0b013e3283540394

Keywords

ARPP-19; microRNA; neurite outgrowth; PP2A

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Funding

  1. NIH [R01 GM49831, T32 GM089626]

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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. NeuroReport 23:590-595 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

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