MICRORNA-29A/PTEN PATHWAY MODULATES NEURITE OUTGROWTH IN PC12 CELLS

PTEN serves as an intrinsic brake on neurite outgrowth, but the regulatory mechanism that governs its action is not clear. In the present study, miR-29a was found to increase neurite outgrowth by decreasing PTEN expression. Results showed that miR-92a-1, miR-29a, miR-92b, and miR-29c expression levels increased during nerve growth factor (NGF)-induced differentiation of PC12 cells. Based on in silico analysis of possible miR-29a targets, PTEN mRNA may be a binding site for miR-29a. A protein expression assay and luciferase reporter assay showed that miR-29a could directly target the 3'-UTRs (untranslated regions) of PTEN mRNA and down-regulate the expression of PTEN. PC12 cells infected with lentiviral pLKO-miR-29a showed far higher levels of miR-29a and Akt phosphorylation level than those infected with control. This promoted neurite outgrowth of PC12 cells. Collectively, these results indicate that miR-29a is an important regulator of neurite outgrowth via targeting PTEN and that it may be a promising therapeutic target for neural disease. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.