MicroRNA-29c/PTEN Pathway is Involved in Mice Brain Development and Modulates Neurite Outgrowth in PC12 Cells

被引:28
|
作者
Zou, Hongjun [1 ]
Ding, Ya [1 ]
Shi, Weifeng [2 ]
Xu, Xu [1 ]
Gong, Aihua [3 ]
Zhang, Zhijian [3 ]
Liu, Jinbo [1 ,4 ]
机构
[1] Suzhou Univ, Affiliated Hosp 3, Dept Orthoped, Peoples Hosp Changzhou 1, Changzhou 213003, Peoples R China
[2] Suzhou Univ, Affiliated Hosp 3, Dept Clin Lab, Changzhou 213003, Peoples R China
[3] Jiangsu Univ, Sch Med, Zhenjiang 212013, Peoples R China
[4] Suzhou Univ, Affiliated Hosp 3, Sch Med, Dept Orthopaed,Peoples Hosp Changzhou 1, Changzhou 213003, Peoples R China
基金
美国国家科学基金会;
关键词
miRNA; Brain development; Neurite outgrowth; miR-29c; PTEN; Akt; PTEN; MIR-29; PROLIFERATION; EXPRESSION; MICRORNAS; NEURONS; DISEASE; CANCER; DIFFERENTIATION; DELETION;
D O I
10.1007/s10571-014-0126-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Growing evidence indicates that microRNAs (miRNAs) are important mediators of brain development and neurite growth. However, the affected signaling mechanisms are not clearly clarified. In the present study, we confirm that miR-29c is expressed during mice brain development and increases neurite outgrowth via decreasing PTEN expression. We first screen the picked-out miR-29c up-regulated in PC12 cells induced by nerve growth factor (NGF). In silico analysis of possible miR-29c targets, VEGFA, MAPK3, PDGFB, and PTEN mRNA are proposed as relatively likely putative binding sites for miR-29c. Subsequently, we detect that miR-29c is involved in brain development and has a negative relationship with the expression of PTEN. Then, using luciferase reporter assay, we demonstrate that miR-29c could directly target to the 3'-UTR of PTEN mRNA and result in down-expression of PTEN. By infecting PC12 cells with lentiviral pLKO-miR-29c or control, we also find that increasing levels of miR-29c markedly increase Akt phosphorylation level, and thus, promote neurite outgrowth of PC12 cells. Together, our results identify that miR-29c is required for mice brain development and modulates neurite outgrowth in PC12 cells via targeting PTEN and has a promising therapeutic target for neural disease.
引用
收藏
页码:313 / 322
页数:10
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