Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140

Nicolás, Francisco E.; Pais, Helio; Schwach, Frank; Lindow, Morten; Kauppinen, Sakari; Moulton, Vincent; Dalmay, Tamás

doi:10.1261/rna.1221108

Cited by 106 publications

(101 citation statements)

References 35 publications

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“…We recently generated mRNA expression profiles of C3H10T1/2 cells following overexpression or suppression of miR-140 (Nicolas et al 2008). This approach identified several direct miR-140 targets that showed higher or lower mRNA levels when the miRNA was silenced or overexpressed, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Several target genes of miR-140 have been identified recently including histone deacetylase 4 (Tuddenham et al 2006), platelet-derived growth factor receptor a (Eberhart et al 2008), CXC group of chemokine ligand 12 (Nicolas et al 2008), and Smad3 is another biologically relevant target gene. The Smad transcription factor family is part of the TGFb pathway (Heldin et al 1997), which plays a role in many diverse biological processes including chondrogenesis and chondrocyte differentiation (Yang et al 2001).…”

Section: Identification and Validation Of Smad3 As A Mir-140 Targetmentioning

confidence: 99%

“…miR-140 overexpression and suppression microarray data are also available on GEO (accession number GSE13590). Differentially expressed genes were obtained as described previously (Nicolas et al 2008). …”

Section: Nucleotide Sequence and Microarray Data Analysismentioning

confidence: 99%

“…We previously profiled mRNAs by Affymetrix microarray following manipulation of the activity of miR-140 in the pluripotent mouse embryonic fibroblast cell line and identified several genes regulated at the RNA and protein levels by miR-140 (Nicolas et al 2008). Here we describe an approach aimed at revealing targets regulated solely at the protein level without proteomics data.…”

Section: Introductionmentioning

confidence: 99%

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Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level

Pais

Nicolás²,

Soond³

et al. 2010

RNA

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110

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mRNA profiling is routinely used to identify microRNA targets, however, this high-throughput technology is not suitable for identifying targets regulated only at protein level. Here, we have developed and validated a novel methodology based on computational analysis of promoter sequences combined with mRNA microarray experiments to reveal transcription factors that are direct microRNA targets at the protein level. Using this approach we identified Smad3, a key transcription factor in the TGFb signaling pathway, as a direct miR-140 target. We showed that miR-140 suppressed the TGFb pathway through repression of Smad3 and that TGFb suppressed the accumulation of miR-140 forming a double negative feedback loop. Our findings establish a valid strategy for the discovery of microRNA targets regulated only at protein level, and we propose that additional targets could be identified by re-analysis of existing microarray datasets.

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Section: Resultsmentioning

confidence: 99%

Section: Identification and Validation Of Smad3 As A Mir-140 Targetmentioning

confidence: 99%

Section: Nucleotide Sequence and Microarray Data Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level

Pais

Nicolás²,

Soond³

et al. 2010

RNA

Self Cite

110

View full text Add to dashboard Cite

show abstract

“…4 6 The subset of miRNA targets that are destabilized in vivo can be identified as downregulated upon induction of the targeting miRNA and vice versa using microarray, qPCR-based or sequencing approaches. [9][10][11][12] miRNAs are implicated in many cancers 13 and have been shown to be useful as biomarkers. 14 The exposure of human cells in tissue culture to various stresses has shown that miRNAs respond to a diversity of external stimuli, 15 indicating important regulatory roles in cellular responses to stress.…”

mentioning

confidence: 99%

MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction

et al. 2012

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Caloric restriction has been shown to increase lifespan in several organisms and to delay onset of age-related diseases. The transcriptional response to caloric restriction has been studied for mRnAs, while the microRnA signature following caloric restriction remains unexplored. here, we characterize the microRnA expression in mouse breast tissue before and after caloric restriction, reporting several changes in the microRnA expression profile. In particular, miR-203 is found to be highly induced by caloric restriction, and we demonstrate that caveolin-1 as well as p63 are direct targets of miR-203 in vivo during caloric restriction. Using tissue culture models, we suggest that this regulation is important in both mouse and human. In conclusion, we show that the microRnA response induced by caloric restriction can regulate important factors in processes such as longevity and aging and is an integral and important component of the cellular response to caloric restriction.Caloric restriction (CR) has been shown to have a positive effect on life span across several organisms [1][2][3] and is speculated to be beneficial for the treatment of age-related diseases. Delineating the genetic response to CR is crucial to understand these effects on aging and disease and specifically in breast tissue since CR has been shown to have potential therapeutic benefit in diseases of the breast. 4,5

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The Emerging Role of Epigenetics in Stroke

Qureshi¹,

Mehler²

2010

Arch Neurol

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ecent scientific advances have demonstrated the existence of extensive RNA-based regulatory networks involved in orchestrating nearly every cellular process in health and various disease states. This previously hidden layer of functional RNAs is derived largely from non-protein-coding DNA sequences that constitute more than 98% of the genome in humans. These non-protein-coding RNAs (ncRNAs) include subclasses that are well known, such as transfer RNAs and ribosomal RNAs, as well as those that have more recently been characterized, such as microRNAs, small nucleolar RNAs, and long ncRNAs. In this review, we examine the role of these novel ncRNAs in the nervous system and highlight emerging evidence that implicates RNAbased networks in the molecular pathogenesis of stroke. We also describe RNA editing, a related epigenetic mechanism that is partly responsible for generating the exquisite degrees of environmental responsiveness and molecular diversity that characterize ncRNAs. In addition, we discuss the development of future therapeutic strategies for locus-specific and genome-wide regulation of genes and functional gene networks through the modulation of RNA transcription, posttranscriptional RNA processing (eg, RNA modifications, quality control, intracellular trafficking, and local and longdistance intercellular transport), and RNA translation. These novel approaches for neural cell-and tissue-selective reprogramming of epigenetic regulatory mechanisms are likely to promote more effective neuroprotective and neural regenerative responses for safeguarding and even restoring central nervous system function.

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Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140

Cited by 106 publications

References 35 publications

Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level

Analyzing mRNA expression identifies Smad3 as a microRNA-140 target regulated only at protein level

MicroRNA-203 regulates caveolin-1 in breast tissue during caloric restriction

The Emerging Role of Epigenetics in Stroke

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