Dataset Information

MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.

ABSTRACT: MicroRNAs (miRNAs) are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In this study, we demonstrate that miR-130a inhibits neurite outgrowth and reduces dendritic spine density as well as dendritic complexity. Bioinformatics analyses, cell cultures and biochemical experiments indicate that miR-130a targets MECP2 and down-regulates MeCP2 protein expression. Furthermore, expression of the wild-type MeCP2, but not a loss-of-function mutant, rescues the miR-130a-induced phenotype. Our study uncovers the MECP2 gene as a previous unknown target for miR-130a, supporting that miR-130a may play a role in neurodevelopment by regulating MeCP2. Together with data from other groups, our work suggests that a feedback regulatory mechanism involving both miR-130a and MeCP2 may serve to ensure their appropriate expression and function in neural development.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4930766 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.

Zhang Yunjia Y Chen Mengmeng M Qiu Zilong Z Hu Keping K McGee Warren W Chen Xiaoping X Liu Jianghong J Zhu Li L Wu Jane Y JY

Protein & cell 20160601 7

MicroRNAs (miRNAs) are critical for both development and function of the central nervous system. Significant evidence suggests that abnormal expression of miRNAs is associated with neurodevelopmental disorders. MeCP2 protein is an epigenetic regulator repressing or activating gene transcription by binding to methylated DNA. Both loss-of-function and gain-of-function mutations in the MECP2 gene lead to neurodevelopmental disorders such as Rett syndrome, autism and MECP2 duplication syndrome. In t ...[more]

PMID: 27245166

Similar Datasets

Project description:BackgroundCerebral stroke induces neuronal dysfunction as a consequence of neuronal morphology changes. Emerging evidence suggests that microRNAs (miRNAs) may play an important role in regulating dysfunction in stroke, yet there are still few studies examining the association between whole blood miRNAs and neuronal morphology. The present study aimed to ascertain the potential roles and mechanisms of action of miR-130a-3p in ischemic stroke.MethodsThe miRNA datasets of peripheral serum in the GEO database and the mRNA datasets of the human brain after ischemia were analyzed to identify differentially expressed RNAs, and their functions were verified in cultured neurons in vitro. Furthermore, the target gene was validated by dual-luciferase reporter assay, RT-PCR, Western blot, and immunofluorescence experiments. The identified miRNA was further verified by the OGD test to restore neuronal changes after ischemia through APP.ResultsThe expression of whole blood miR-130a-3p was found significantly lower in participants with ischemic stroke than in controls by analyzing expression profiling datasets of cerebral ischemia stroke obtained from the Gene Expression Omnibus (GEO) DataSets portal, which was confirmed in the MCAO model in mice. Furthermore, GO analysis showed that miR-130a-3p might directly affect neuronal function. Indeed, we demonstrated that miR-130a-3p played a central role in the inhibition of dendritic morphogenesis and in the growth of dendritic spines in vitro. We also confirmed that miR-130a-3p could regulate the expression of APP by luciferase reporter assay, RT-PCR, Western blot, and immunofluorescence experiments, which were consistent with the bioinformatic analysis. Last but not least, we also demonstrated that reducing miR-130a-3p expression partially rescued neuronal morphological changes after OGD in vitro.ConclusionmiR-130a-3p is a potential biomarker of cerebral stroke, can affect neuronal morphology through APP, and promote the repair of neurons by promoting APP expression after cerebral ischemia.

Dataset Information

MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.

Publications

MiR-130a regulates neurite outgrowth and dendritic spine density by targeting MeCP2.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets