The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development

Visvanathan, Jaya; Lee, Seung‐Hee; Lee, Bora; Lee, Jae Woo; Lee, Soo Kyung

doi:10.1101/gad.1519107

Cited by 616 publications

(579 citation statements)

References 39 publications

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“…They found that the mRNA for the splicing factor PTBP1 is a direct target of miR-124 repression, and that part of the effects of miR-124 could be attributed to alternate mRNA splicing arising from the downregulation of PTBP1. Visvanathan et al [46] also reported that miR-124 function in the embryonic chicken neural tube promoted neuronal differentiation and cell cycle exit, while Krichevsky et al [45] found that coexpression of miR-124 and miR-9 in ES cells differentiated in vitro increased the fraction of neuronal cells. Previous studies demonstrated that miR-124 is likely to downregulate the level of numerous direct target mRNAs [41,42], as well as indirectly upregulate neuronal transcription by inhibition of the REST/NRSF transcriptional repressor complex [43,46].…”

Section: Discussionmentioning

confidence: 99%

“…The expression of miR-124 appears in part to mediate the repression of non-neuronal genes in neurons [41][42][43], as well as the downregulation of genes expressed in neural progenitors [44]. Overexpression of miR-124 (and other brain-enriched miRNAs) in mouse embryonic stem cells promotes neuronal fates [45], and a recent study indicates that miR-124 can promote neuronal differentiation via inhibition of the Ctdsp1/SCP1 phosphatase, a component of the REST/NRSF transcriptional repression complex [46]. miR-124 can also target PTBP1, a global repressor of alternative splicing, thereby regulating alternative splicing during neuronal differentiation [47].…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

Chung

Deo

et al. 2008

Experimental Cell Research

292

211

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MicroRNAs (miRNAs) are small RNAs with diverse regulatory roles. The miR-124 miRNA is expressed in neurons in the developing and adult nervous system. Here we show that overexpression of miR-124 in differentiating mouse P19 cells promotes neurite outgrowth, while blocking miR-124 function delays neurite outgrowth and decreases acetylated α-tubulin. Altered neurite outgrowth also was observed in mouse primary cortical neurons when miR-124 expression was increased, or when miR-124 function was blocked. In uncommitted P19 cells, miR-124 expression led to disruption of actin filaments and stabilization of microtubules. Expression of miR-124 also decreased Cdc42 protein and affected the subcellular localization of Rac1, suggesting that miR-124 may act in part via alterations to members of the Rho GTPase family. Furthermore, constitutively active Cdc42 or Rac1 attenuated neurite outgrowth promoted by miR-124. To obtain a broader perspective, we identified mRNAs downregulated by miR-124 in P19 cells using microarrays. mRNAs for proteins involved in cytoskeletal regulation were enriched among mRNAs downregulated by miR-124. A miR-124 variant with an additional 5' base failed to promote neurite outgrowth and downregulated substantially different mRNAs. These results indicate that miR-124 contributes to the control of neurite outgrowth during neuronal differentiation, possibly by regulation of the cytoskeleton.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

Chung

Deo

et al. 2008

Experimental Cell Research

292

211

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“…It is highly likely that this circuitry is disrupted in cancer differentiating neurons. 55 SCP1 is an antineural factor that acts as a part of the REST complex to prevent the expression of neural genes in nonneural tissues. 56 This results in the establishment of a double-negative feedback loop between miR-124 and the REST complex.…”

Section: Micrornas In Glioblastomamentioning

confidence: 99%

MicroRNAs and glioblastoma; the stem cell connection

et al. 2009

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Recent data draw close parallels between cancer, including glial brain tumors, and the biology of stem and progenitor cells. At the same time, it has become clear that one of the major roles that microRNAs play is in the regulation of stem cell biology, differentiation, and cell 'identity'. For example, microRNAs have been increasingly implicated in the regulation of neural differentiation. Interestingly, initial studies in the incurable brain tumor glioblastoma multiforme strongly suggest that microRNAs involved in neural development play a role in this disease. This encourages the idea that certain miRs allow continued tumor growth through the suppression of differentiation and the maintenance of the stem cell-like properties of tumor cells. These concepts will be explored in this article.

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“…But miR-124 expression is absent in non-neuronal cells, even neuronal progenitor cells. A negative feedback loop operates between miR-124 and SCP1/REST pathway that decides neural or anti-neural behavior of the cell [10,11].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes

Das

Bhattacharyya

2014

FEBS Letters

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Edited by Tamas Dalmay Keywords:MicroRNA-432 NESTIN RCOR1 MECP2 Neurite outgrowth SH-SY5Y cells a b s t r a c t MicroRNA (miRNA) regulates expression of protein coding genes and has been implicated in diverse cellular processes including neuronal differentiation, cell growth and death. To identify the role of miRNA in neuronal differentiation, SH-SY5Y and IMR-32 cells were treated with dopamine cocktail and retinoic acid to induce differentiation. Detection of miRNAs in differentiated cells revealed that expression of many miRNAs was altered significantly. Among the altered miRNAs, human brain expressed miR-432 induced neurite projections, arrested cells in G0-G1, reduced cell proliferation and could significantly repress NESTIN/NES, RCOR1/COREST and MECP2. Our results reveal that miR-432 regulate neuronal differentiation of human neuroblastoma cells.

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The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development

Cited by 616 publications

References 39 publications

MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

MicroRNA miR-124 regulates neurite outgrowth during neuronal differentiation

MicroRNAs and glioblastoma; the stem cell connection

MicroRNA‐432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes

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