MiR-125b orchestrates cell proliferation, differentiation and migration in neural stem-progenitor cells by targeting NestinReportar como inadecuado




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BMC Neuroscience

, 13:116

First Online: 28 September 2012Received: 23 March 2012Accepted: 17 September 2012

Abstract

BackgroundThe emerging concept is that microRNAs miRNAs play a central role in controlling stem cell self-renewal and fate determination by regulating the expression of stem cell regulators. miR-125b, one of neuronal miRNAs, recently was found to be necessary for neural differentiation of neural stem-progenitor cells NS-PCs. However, the other specific biological role of miR-125b in NS-PCs is little known. We used rat NS-PCs as a model system to study the role of miR-125b in governing the behavior of NS-PCs.

ResultsWe report here the transfection of exogenous miR-125b inhibited proliferation of NS-PCs but promoted differentiation and migration. Whereas anti-miR-125b had the opposite effect. Similar results were observed when Nestin was knocked down by siRNA. Subsequently, we demonstrated that Nestin was a direct functional target of miR-125b. MiR-125b downregulates the expression of luciferase through Nestin 3’untranslated region 3’-UTR, and the regulation was abolished by mutations in the miR-125b binding site. MiR-125b targeted the 3-UTR of Nestin and reduced the abundance of Nestin at both mRNA and protein levels.

ConclusionThe results provided new insight into the function by which miR-125b modulates NS-PCs proliferation, differentiation and migration. The data also indicated the regulatory role of miR-125b in NS-PCs might through the suppression of Nestin expression.

KeywordsNeural stem-progenitor cells MiR-125b Nestin AbbreviationsmiRNAsMicroRNAs

mRNAMessenger RNA

NS-PCsNeural stem and progenitor cells

3’-UTR3’ untranslated region

CNSCentral nervous system

ES cellsEmbryonic stem cells

EC cellsEmbryocarcinoma cells

NCNegative control

INNCInhibitor negative control

BrdUBromodeoxyuridine

FAM6-carboxy-fluo-rescine

RNAiRNA interference

SiRNASmall interfering RNA

DMEMDulbecco-s modified Eagle-s medium

FBSFetal bovine serum

EGFEpidermal growth factor

BFGFBasic fibroblast growth factor

TBStris-buffered saline

PBSPhosphate-buffered saline

FITCFluoresceinisothiocyanate

SCFStem cell factor

ANOVAAnalysis of variance.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-13-116 contains supplementary material, which is available to authorized users.

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Autor: Yi Cui - Zhifeng Xiao - Jin Han - Jie Sun - Wenyong Ding - Yannan Zhao - Bing Chen - Xiaoran Li - Jianwu Dai

Fuente: https://link.springer.com/







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