Selenium alters miRNA profile in an intestinal cell line: Evidence that miR‐185 regulates expression of <i>GPX2</i> and <i>SEPSH2</i>

Maciel-Dominguez, Anabel; Swan, Daniel; Ford, Dianne; Hesketh, John E.

doi:10.1002/mnfr.201300168

Cited by 64 publications

(41 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another possible mechanism is the recently discovered regulation of selenoprotein by miRNAs: mi-185 has been shown to have an effect on GPX2 and SPS2. Since NMD cannot explain the experimental observations for SPS2, it is possible that miRNA regulation is the dominant mechanism for this selenoprotein (Maciel-Dominguez et al 2013).…”

Section: Discussionmentioning

confidence: 96%

Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy

Županič

Méplan

Huguenin

et al. 2016

RNA

View full text Add to dashboard Cite

The expression of selenoproteins, a specific group of proteins that incorporates selenocysteine, is hierarchically regulated by the availability of Se, with some, but not all selenoprotein mRNA transcripts decreasing in abundance with decreasing Se. Selenocysteine insertion into the peptide chain occurs during translation following recoding of an internal UGA stop codon. There is increasing evidence that this UGA recoding competes with premature translation termination, which is followed by nonsense-mediated decay (NMD) of the transcript. In this study, we tested the hypothesis that the susceptibility of different selenoprotein mRNAs to premature termination during translation and differential sensitivity of selenoprotein transcripts to NMD are major factors in the selenoprotein hierarchy. Selenoprotein transcript abundance was measured in Caco-2 cells using real-time PCR under different Se conditions and the data obtained fitted to mathematical models of selenoprotein translation. A calibrated model that included a combination of differential sensitivity of selenoprotein transcripts to NMD and different frequency of non-NMD related premature translation termination was able to fit all the measurements. The model predictions were tested using SiRNA to knock down expression of the crucial NMD factor UPF1 (up-frameshift protein 1) and selenoprotein mRNA expression. The calibrated model was able to predict the effect of UPF1 knockdown on gene expression for all tested selenoproteins, except SPS2 (selenophosphate synthetase), which itself is essential for selenoprotein synthesis. These results indicate an important role for NMD in the hierarchical regulation of selenoprotein mRNAs, with the exception of SPS2 whose expression is likely regulated by a different mechanism.

show abstract

Section: Discussionmentioning

confidence: 96%

Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy

Županič

Méplan

Huguenin

et al. 2016

RNA

View full text Add to dashboard Cite

show abstract

“…Microarray analysis (737 miRNAs in total) of the miRNA profiles of Caco-2 cells grown in Se-deficient or Se-supplemented medium revealed that the expression of 12 miRNAs was affected by Se supply. 80 Expression levels of 50 mRNAs were also Se-responsive in the same study, and numerous of these mRNAs were predicted to be targeted by the Se-responsive miRNAs. One of these, miRNA-185, whose expression decreased under Se deficiency, was confirmed to regulate expression of glutathione peroxidase 2 (GPx-2) and selenophosphate synthetase 2 (SPS-2).…”

Section: Regulation Of Microrna Expression By Seleniummentioning

confidence: 74%

Epigenetic effects of selenium and their implications for health

2015

View full text Add to dashboard Cite

“…In the particular case of nutritranscriptomics, sample availability is more restricted than in the rest of the omics since biological fluids lack cells for RNA extraction, and as such is useful only tissue biopsies or cell lines. For this reason, the use of animal and cellular models has provided valuable insights on gene expression responses to different nutrients or energy restriction (Maciel-Dominguez et al, 2013;Shahzad et al, 2014), circumventing the well-known drawbacks inherent in studies requiring human samples. Shahzad et al (2014) generated transcriptome data from overfed (OF) or restricted fed (RE) cows to evaluate the impact of energy intake on cow livers during the peripartal period.…”

Section: Nutritranscriptomicsmentioning

confidence: 99%

“…PPARs, SREBPs and NFE2L2) in priming the liver of RE cows to better adapt to the early postpartum metabolic and inflammatory challenges (Shahzad et al, 2014). Maciel-Dominguez et al (2013) compared gene expression profiles of wild-type and peroxisome proliferator-activated receptor deficient mice (PPARÀ/À mice) fed with specific fatty acids to assess their role in heart tissue and the implications of PPARa. This study showed several genes statistically regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g.…”

Section: Nutritranscriptomicsmentioning

confidence: 99%

Discovery of nutritional biomarkers: future directions based on omics technologies

Odriozola

Corrales

2015

International Journal of Food Sciences and Nutrition

View full text Add to dashboard Cite

Understanding the interactions between food and human biology is of utmost importance to facilitate the development of more efficient nutritional interventions that might improve our wellness status and future health outcomes by reducing risk factors for non-transmittable chronic diseases, such as cardiovascular diseases, cancer, obesity and metabolic syndrome. Dissection of the molecular mechanisms that mediate the physiological effects of diets and bioactive compounds is one of the main goals of current nutritional investigation and the food industry as might lead to the discovery of novel biomarkers. It is widely recognized that the availability of robust nutritional biomarkers represents a bottleneck that delays the innovation process of the food industry. In this regard, omics sciences have opened up new avenues of research and opportunities in nutrition. Advances in mass spectrometry, nuclear magnetic resonance, next generation sequencing and microarray technologies allow massive genome, gene expression, proteomic and metabolomic profiling, obtaining a global and in-depth analysis of physiological/pathological scenarios. For this reason, omics platforms are most suitable for the discovery and characterization of novel nutritional markers that will define the nutritional status of both individuals and populations in the near future, and to identify the nutritional bioactive compounds responsible for the health outcomes.

show abstract

Selenium alters miRNA profile in an intestinal cell line: Evidence that miR‐185 regulates expression of GPX2 and SEPSH2

Abstract: We propose that miR-185 plays a role in up-regulation of GPX2 and SEPHS2 expression. In the case of SEPHS2 this may contribute to maintaining selenoprotein synthesis. The data indicate that micronutrient supply can regulate the cell miRNA expression profile.

Cited by 64 publications

References 51 publications

Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy

Modeling and gene knockdown to assess the contribution of nonsense-mediated decay, premature termination, and selenocysteine insertion to the selenoprotein hierarchy

Epigenetic effects of selenium and their implications for health

Discovery of nutritional biomarkers: future directions based on omics technologies

Contact Info

Product

Resources

About