Limits...
Use of miRNAs in biofluids as biomarkers in dietary and lifestyle intervention studies.

Rome S - Genes Nutr (2015)

Bottom Line: It is believed that noncoding RNAs, such as circulating microRNAs (miRNAs), may represent such a new class of integrative biomarkers.In addition, a number of recent studies also indicate that miRNAs could permit to monitor the impact of diet on gut microbiota.We also discuss the main preanalytical considerations that are important to take into account before miRNA screening which can affect the reproducibility of the data.

View Article: PubMed Central - PubMed

Affiliation: CarMeN Laboratory (INSERM 1060, INRA 1397, INSA), Faculté de Médecine Lyon-Sud, University of Lyon, Chemin du Grand Revoyet, 69600, Oullins, France, srome@univ-lyon1.fr.

ABSTRACT
The selection of biomarkers in nutrigenomics needs to reflect subtle changes in homoeostasis representing the relation between nutrition and health, or nutrition and disease. It is believed that noncoding RNAs, such as circulating microRNAs (miRNAs), may represent such a new class of integrative biomarkers. Until now, the most relevant body fluids for miRNA quantification in response to nutrition have not been clearly defined, but recent studies listed in this review indicate that miRNAs from plasma or serum, PBMC and faeces might be relevant biomarkers to quantify the physiological impacts of dietary or lifestyle intervention studies. In addition, a number of recent studies also indicate that miRNAs could permit to monitor the impact of diet on gut microbiota. We also discuss the main preanalytical considerations that are important to take into account before miRNA screening which can affect the reproducibility of the data.

No MeSH data available.


Related in: MedlinePlus

Origin of the different populations of extracellular miRNAs in biofluids. (1) In the nucleus, miRNA genes are transcribed by the RNA polymerase II into primary miRNAs (pri-miRNAs) from DNA and processed by the Drosha complex (pre-miRNAs). pre-miRNAs are exported to the cytoplasm and cleaved by Dicer to produce a double-stranded miRNA duplex. The duplex is separated, and a mature miRNA is incorporated into the RNA-induced silencing complex (RISC). Within the RISC complex, miRNAs bind to their target messenger RNAs (mRNAs) to repress their translation or induce their degradation. In the cytoplasm, pre-miRNAs and mature miRNAs can also be incorporated into small vesicles called exosomes, which are released from cells when multivesicular bodies (MVB) fuse with the plasma membrane (2). Pre-miRNA or mature miRNA can also be released through blebbing of the plasma membrane (microparticles) (3) or during cell apoptosis in apoptotic bodies (4). miRNAs are also found in circulation in vesicle-free form. These miRNAs can be associated with high-density lipoproteins (HDL) (5) or bound to RNA-binding proteins (RNP) (6). In addition, miRNAs may be released actively, in an miRNA-specific manner, through interaction with specific membrane channels or proteins (7)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4522245&req=5

Fig1: Origin of the different populations of extracellular miRNAs in biofluids. (1) In the nucleus, miRNA genes are transcribed by the RNA polymerase II into primary miRNAs (pri-miRNAs) from DNA and processed by the Drosha complex (pre-miRNAs). pre-miRNAs are exported to the cytoplasm and cleaved by Dicer to produce a double-stranded miRNA duplex. The duplex is separated, and a mature miRNA is incorporated into the RNA-induced silencing complex (RISC). Within the RISC complex, miRNAs bind to their target messenger RNAs (mRNAs) to repress their translation or induce their degradation. In the cytoplasm, pre-miRNAs and mature miRNAs can also be incorporated into small vesicles called exosomes, which are released from cells when multivesicular bodies (MVB) fuse with the plasma membrane (2). Pre-miRNA or mature miRNA can also be released through blebbing of the plasma membrane (microparticles) (3) or during cell apoptosis in apoptotic bodies (4). miRNAs are also found in circulation in vesicle-free form. These miRNAs can be associated with high-density lipoproteins (HDL) (5) or bound to RNA-binding proteins (RNP) (6). In addition, miRNAs may be released actively, in an miRNA-specific manner, through interaction with specific membrane channels or proteins (7)

Mentions: MicroRNAs (miRNAs) are a class of evolutionally conserved noncoding RNAs of 19–22 nucleotides and function as negative regulators of gene expression. Originally discovered in C. elegans, miRNAs regulate fundamental cellular processes in diverse organisms (Lagos-Quintana et al. 2001; Lee and Ambros 2001). miRNAs are encoded within the genome (from intronic, exonic or intergenic regions) and are initially transcribed as primary transcripts that can be several kilobases in length (pri-miR) (Fig. 1). Primary transcripts are successively cleaved by two RNase III enzymes, Drosha in the nucleus and Dicer in the cytoplasm, to produce 70 nucleotide long precursor miRNAs (pre-miR) and then mature miRNAs, respectively. Single-stranded mature miRNAs associate with Argonaute proteins (Ago) to form the core of a multicomponent gene regulatory complex named the RNA-induced silencing complex (RISC) (Bartel 2004). Three mechanisms have been described for gene regulation via miRNA (1) translation repression, (2) direct mRNA degradation (III) and miRNA-mediated mRNA decay. Recent data have suggested that the mechanism of repression is predominately via a decrease in mRNA target stability (Guo et al. 2011). miRNA activity and abundance is also regulated on various levels ranging from transcription and processing to target site binding and miRNA stability (Treiber et al. 2012). Bioinformatic analyses indicate that miRNAs can regulate multiple target mRNAs (i.e. nearly 60 % of all mammalian mRNAs represent miRNA targets) and individual mRNA can be targeted by several miRNAs (Lewis et al. 2003). Functional analysis of miRNA target genes has shown that they play a major role in the regulation of developmental processes including cell growth and differentiation and programmed cell death by targeting preferential signalling pathways and transcription factors (Stark et al. 2005; Cui et al. 2006, 2007). In addition, important roles of miRNAs have emerged in the control of metabolic pathways involved in lipid metabolism, adipocyte differentiation, energy homoeostasis, glucose-stimulated insulin secretion and inflammation (Lynn 2009). Thus, as a consequence of the widespread range of processes they are able to influence, miRNA deregulation is a hallmark of several pathological conditions, including cancer (Lages et al. 2012), inflammation (O’Connell et al. 2011), neurological disorders (Salta and De Strooper 2012), cardiovascular diseases and metabolic disorders (Lorenzen et al. 2010). Studies during the last 5 years have also demonstrated that dietary compounds such as amino acids, carbohydrates, fatty acids and vitamins can lead to changes in miRNA expressions and affect their functions (Garcia-Segura et al. 2013), making them good candidates to study, at the tissue or cellular level, the response of a specific nutrient or diet (Garcia-Segura et al. 2013).Fig. 1


Use of miRNAs in biofluids as biomarkers in dietary and lifestyle intervention studies.

Rome S - Genes Nutr (2015)

Origin of the different populations of extracellular miRNAs in biofluids. (1) In the nucleus, miRNA genes are transcribed by the RNA polymerase II into primary miRNAs (pri-miRNAs) from DNA and processed by the Drosha complex (pre-miRNAs). pre-miRNAs are exported to the cytoplasm and cleaved by Dicer to produce a double-stranded miRNA duplex. The duplex is separated, and a mature miRNA is incorporated into the RNA-induced silencing complex (RISC). Within the RISC complex, miRNAs bind to their target messenger RNAs (mRNAs) to repress their translation or induce their degradation. In the cytoplasm, pre-miRNAs and mature miRNAs can also be incorporated into small vesicles called exosomes, which are released from cells when multivesicular bodies (MVB) fuse with the plasma membrane (2). Pre-miRNA or mature miRNA can also be released through blebbing of the plasma membrane (microparticles) (3) or during cell apoptosis in apoptotic bodies (4). miRNAs are also found in circulation in vesicle-free form. These miRNAs can be associated with high-density lipoproteins (HDL) (5) or bound to RNA-binding proteins (RNP) (6). In addition, miRNAs may be released actively, in an miRNA-specific manner, through interaction with specific membrane channels or proteins (7)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4522245&req=5

Fig1: Origin of the different populations of extracellular miRNAs in biofluids. (1) In the nucleus, miRNA genes are transcribed by the RNA polymerase II into primary miRNAs (pri-miRNAs) from DNA and processed by the Drosha complex (pre-miRNAs). pre-miRNAs are exported to the cytoplasm and cleaved by Dicer to produce a double-stranded miRNA duplex. The duplex is separated, and a mature miRNA is incorporated into the RNA-induced silencing complex (RISC). Within the RISC complex, miRNAs bind to their target messenger RNAs (mRNAs) to repress their translation or induce their degradation. In the cytoplasm, pre-miRNAs and mature miRNAs can also be incorporated into small vesicles called exosomes, which are released from cells when multivesicular bodies (MVB) fuse with the plasma membrane (2). Pre-miRNA or mature miRNA can also be released through blebbing of the plasma membrane (microparticles) (3) or during cell apoptosis in apoptotic bodies (4). miRNAs are also found in circulation in vesicle-free form. These miRNAs can be associated with high-density lipoproteins (HDL) (5) or bound to RNA-binding proteins (RNP) (6). In addition, miRNAs may be released actively, in an miRNA-specific manner, through interaction with specific membrane channels or proteins (7)
Mentions: MicroRNAs (miRNAs) are a class of evolutionally conserved noncoding RNAs of 19–22 nucleotides and function as negative regulators of gene expression. Originally discovered in C. elegans, miRNAs regulate fundamental cellular processes in diverse organisms (Lagos-Quintana et al. 2001; Lee and Ambros 2001). miRNAs are encoded within the genome (from intronic, exonic or intergenic regions) and are initially transcribed as primary transcripts that can be several kilobases in length (pri-miR) (Fig. 1). Primary transcripts are successively cleaved by two RNase III enzymes, Drosha in the nucleus and Dicer in the cytoplasm, to produce 70 nucleotide long precursor miRNAs (pre-miR) and then mature miRNAs, respectively. Single-stranded mature miRNAs associate with Argonaute proteins (Ago) to form the core of a multicomponent gene regulatory complex named the RNA-induced silencing complex (RISC) (Bartel 2004). Three mechanisms have been described for gene regulation via miRNA (1) translation repression, (2) direct mRNA degradation (III) and miRNA-mediated mRNA decay. Recent data have suggested that the mechanism of repression is predominately via a decrease in mRNA target stability (Guo et al. 2011). miRNA activity and abundance is also regulated on various levels ranging from transcription and processing to target site binding and miRNA stability (Treiber et al. 2012). Bioinformatic analyses indicate that miRNAs can regulate multiple target mRNAs (i.e. nearly 60 % of all mammalian mRNAs represent miRNA targets) and individual mRNA can be targeted by several miRNAs (Lewis et al. 2003). Functional analysis of miRNA target genes has shown that they play a major role in the regulation of developmental processes including cell growth and differentiation and programmed cell death by targeting preferential signalling pathways and transcription factors (Stark et al. 2005; Cui et al. 2006, 2007). In addition, important roles of miRNAs have emerged in the control of metabolic pathways involved in lipid metabolism, adipocyte differentiation, energy homoeostasis, glucose-stimulated insulin secretion and inflammation (Lynn 2009). Thus, as a consequence of the widespread range of processes they are able to influence, miRNA deregulation is a hallmark of several pathological conditions, including cancer (Lages et al. 2012), inflammation (O’Connell et al. 2011), neurological disorders (Salta and De Strooper 2012), cardiovascular diseases and metabolic disorders (Lorenzen et al. 2010). Studies during the last 5 years have also demonstrated that dietary compounds such as amino acids, carbohydrates, fatty acids and vitamins can lead to changes in miRNA expressions and affect their functions (Garcia-Segura et al. 2013), making them good candidates to study, at the tissue or cellular level, the response of a specific nutrient or diet (Garcia-Segura et al. 2013).Fig. 1

Bottom Line: It is believed that noncoding RNAs, such as circulating microRNAs (miRNAs), may represent such a new class of integrative biomarkers.In addition, a number of recent studies also indicate that miRNAs could permit to monitor the impact of diet on gut microbiota.We also discuss the main preanalytical considerations that are important to take into account before miRNA screening which can affect the reproducibility of the data.

View Article: PubMed Central - PubMed

Affiliation: CarMeN Laboratory (INSERM 1060, INRA 1397, INSA), Faculté de Médecine Lyon-Sud, University of Lyon, Chemin du Grand Revoyet, 69600, Oullins, France, srome@univ-lyon1.fr.

ABSTRACT
The selection of biomarkers in nutrigenomics needs to reflect subtle changes in homoeostasis representing the relation between nutrition and health, or nutrition and disease. It is believed that noncoding RNAs, such as circulating microRNAs (miRNAs), may represent such a new class of integrative biomarkers. Until now, the most relevant body fluids for miRNA quantification in response to nutrition have not been clearly defined, but recent studies listed in this review indicate that miRNAs from plasma or serum, PBMC and faeces might be relevant biomarkers to quantify the physiological impacts of dietary or lifestyle intervention studies. In addition, a number of recent studies also indicate that miRNAs could permit to monitor the impact of diet on gut microbiota. We also discuss the main preanalytical considerations that are important to take into account before miRNA screening which can affect the reproducibility of the data.

No MeSH data available.


Related in: MedlinePlus