Dataset Information

MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development.

ABSTRACT: MicroRNAs (miRNAs) are important regulators of mouse brain development. However, their precise roles in this context remain to be elucidated. Through screening of expression profiles from a miRNA microarray and experimental analysis, we show here that miR-15b controls several aspects of cortical neurogenesis. miR-15b inhibits cortical neural progenitor cell (NPC) proliferation and promotes cell-cycle exit and neuronal differentiation. Additionally, miR-15b expression decreases the number of apical progenitors and increases basal progenitors in the VZ/SVZ. We also show that miR-15b binds to the 3' UTR of TET3, which plays crucial roles during embryonic development by enhancing DNA demethylation. TET3 promotes cyclin D1 expression, and miR-15b reduces TET3 expression and 5hmC levels. Notably, TET3 expression rescues miR-15b-induced impaired NPC proliferation and increased cell-cycle exit in vivo. Our results not only reveal a link between miRNAs, TET, and DNA demethylation but also demonstrate critical roles for miR-15b and TET3 in maintaining the NPC pool during early neocortical development.

SUBMITTER: Lv X

PROVIDER: S-EPMC4264933 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development.

Lv Xiaohui X Jiang Huihui H Liu Yanli Y Lei Xuepei X Jiao Jianwei J

EMBO reports 20141024 12

MicroRNAs (miRNAs) are important regulators of mouse brain development. However, their precise roles in this context remain to be elucidated. Through screening of expression profiles from a miRNA microarray and experimental analysis, we show here that miR-15b controls several aspects of cortical neurogenesis. miR-15b inhibits cortical neural progenitor cell (NPC) proliferation and promotes cell-cycle exit and neuronal differentiation. Additionally, miR-15b expression decreases the number of apic ...[more]

PMID: 25344561

Similar Datasets

Project description:Glioma is one of the most common, rapidly progressive and fatal brain tumors, and accumulating evidence shows that microRNAs (miRNAs) play important roles in the development of cancers, including glioma. Therapeutic applications of miRNAs in Ras-driven glioma have been proposed; however, their specific functions and mechanisms are poorly understood. Here, we report that miR-1301-3p directly targets the neuroblastoma Ras viral oncogene homolog (N-Ras) and functions as a tumor-suppressor in glioma. Quantitative reverse transcription-PCR was applied to detect the expression of miR-1301-3p in glioma specimens. The direct target genes of miR-1301-3p were predicted by bioinformatic analysis and further verified by immunoblotting and luciferase assays. The effects of miR-1301-3p on the proliferation and cell cycle of glioma cells were analyzed by cell-counting kit 8, colony formation, 5-ethynyl-2-deoxyuridine (EDU) and flow cytometry assays. A xenograft model was used to study the effect of miR-1301-3p on tumor growth and angiogenesis. The expression levels of miR-1301-3p in glioma specimens were significantly downregulated. N-Ras was confirmed as a direct target of miR-1301-3p. MiR-1301-3p inhibited glioma cell growth and blocked the cell cycle to G1 by negatively regulating N-Ras and its downstream signaling pathway, MEK-ERK1/2. Furthermore, the inhibitory effects of miR-1301-3p could be rescued by the overexpression of N-Ras. The protein levels of N-Ras were up-regulated in clinical glioma specimens and were negatively correlated with miR-1301-3p expression levels (r=-056, P=0.0002). In vivo studies revealed that increased levels of miR-1301-3p delayed the growth of intracranial tumors, which was accompanied by decreased Ki67 and CD31 expression. Taken together, our results demonstrate that miR-1301-3p plays a significant role in inactivating the Ras signaling pathway through the inhibition of N-Ras, which may provide a novel therapeutic strategy for treatment of glioma and other Ras-driven cancers.

Dataset Information

MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development.

Publications

MicroRNA-15b promotes neurogenesis and inhibits neural progenitor proliferation by directly repressing TET3 during early neocortical development.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets