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Food Deprivation Affects the miRNome in the Lactating Goat Mammary Gland.

Mobuchon L, Marthey S, Le Guillou S, Laloë D, Le Provost F, Leroux C - PLoS ONE (2015)

Bottom Line: Among the putative targets, 19 were previously identified as differently expressed genes (DEG).The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France; INRA, UMR1213 Herbivores, F-63122, Saint Genès Champanelle, France; Clermont Université, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

ABSTRACT

Background: Nutrition affects milk composition thus influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not fully understood. MicroRNAs (miRNA) are small non coding RNA which are important post-transcriptional regulators of gene expression by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, which may provide clues to deciphering regulations of the biosynthesis and secretion of milk components.

Methodology/principal findings: Using high-throughput sequencing technology, miRNomes of the lactating mammary gland were established from lactating goats fed ad libitum or deprived of food for 48 h affecting milk production and composition. High throughput miRNA sequencing revealed 30 miRNA with an expression potentially modulated by food deprivation; 16 were down-regulated and 14 were up-regulated. Diana-microT predictive tools suggested a potential role for several nutriregulated miRNA in lipid metabolism. Among the putative targets, 19 were previously identified as differently expressed genes (DEG). The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.

Conclusion/significance: In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland. Characterization of these 30 miRNA could contribute to a clearer understanding of gene regulation in the mammary gland in response to nutrition.

No MeSH data available.


Molecular and cellular functions of potentially targeted genes by the 30 nutriregulated miRNA.Data were analysed through the use of QIAGEN’s Ingenuity Pathway Analysis (IPA®, QIAGEN Redwood City, www.qiagen.com/ingenuity).
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pone.0140111.g002: Molecular and cellular functions of potentially targeted genes by the 30 nutriregulated miRNA.Data were analysed through the use of QIAGEN’s Ingenuity Pathway Analysis (IPA®, QIAGEN Redwood City, www.qiagen.com/ingenuity).

Mentions: Among the 30 miRNA that were regulated in our model, only a few have previously been described in the mammary gland. In the mouse mammary gland, miR-126-3p may inhibit cell proliferation; it may also regulate the expression of CSN2 coding for β-casein, one of the major milk proteins, and PGR (ProGesteron Receptor) protein [44]. In addition, miR-99a-5p has been described as a modulator of the TGF β pathway affecting epithelial-to-mesenchyme transition in normal mouse mammary gland [45]. Therefore, in order to investigate the functional role of the 30 nutriregulated miRNA in the mammary gland, target gene predictions were performed based on miRNA/mRNA interactions using Diana-microT v5.0 for known miRNA and TargetScan Custom v5.2 for predicted miRNA. Because no predictive tools have so far been designed for ruminants, conservation between goat miRNA and humans was checked, particularly concerning the seed region that determines miRNA interactions with mRNA targets. Thus, 7,129 different putative targets for the 30 nutriregulated miRNA were identified. Investigating the molecular and cellular functions of these targets using Ingenuity Pathway Analysis revealed that “gene expression”, “cellular development” and “cellular growth and proliferation” were the three pathways most significantly targeted (Fig 2). These findings suggest that food deprivation might lead to a change in gene expression through the actions of miRNA linked to cellular growth and proliferation, as well as the remodelling of mammary cells, as has been observed in this organ in the event of nutrient restriction [46].


Food Deprivation Affects the miRNome in the Lactating Goat Mammary Gland.

Mobuchon L, Marthey S, Le Guillou S, Laloë D, Le Provost F, Leroux C - PLoS ONE (2015)

Molecular and cellular functions of potentially targeted genes by the 30 nutriregulated miRNA.Data were analysed through the use of QIAGEN’s Ingenuity Pathway Analysis (IPA®, QIAGEN Redwood City, www.qiagen.com/ingenuity).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608672&req=5

pone.0140111.g002: Molecular and cellular functions of potentially targeted genes by the 30 nutriregulated miRNA.Data were analysed through the use of QIAGEN’s Ingenuity Pathway Analysis (IPA®, QIAGEN Redwood City, www.qiagen.com/ingenuity).
Mentions: Among the 30 miRNA that were regulated in our model, only a few have previously been described in the mammary gland. In the mouse mammary gland, miR-126-3p may inhibit cell proliferation; it may also regulate the expression of CSN2 coding for β-casein, one of the major milk proteins, and PGR (ProGesteron Receptor) protein [44]. In addition, miR-99a-5p has been described as a modulator of the TGF β pathway affecting epithelial-to-mesenchyme transition in normal mouse mammary gland [45]. Therefore, in order to investigate the functional role of the 30 nutriregulated miRNA in the mammary gland, target gene predictions were performed based on miRNA/mRNA interactions using Diana-microT v5.0 for known miRNA and TargetScan Custom v5.2 for predicted miRNA. Because no predictive tools have so far been designed for ruminants, conservation between goat miRNA and humans was checked, particularly concerning the seed region that determines miRNA interactions with mRNA targets. Thus, 7,129 different putative targets for the 30 nutriregulated miRNA were identified. Investigating the molecular and cellular functions of these targets using Ingenuity Pathway Analysis revealed that “gene expression”, “cellular development” and “cellular growth and proliferation” were the three pathways most significantly targeted (Fig 2). These findings suggest that food deprivation might lead to a change in gene expression through the actions of miRNA linked to cellular growth and proliferation, as well as the remodelling of mammary cells, as has been observed in this organ in the event of nutrient restriction [46].

Bottom Line: Among the putative targets, 19 were previously identified as differently expressed genes (DEG).The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland.

View Article: PubMed Central - PubMed

Affiliation: INRA, UMR1313 Génétique Animale et Biologie Intégrative, F-78350, Jouy-en-Josas, France; INRA, UMR1213 Herbivores, F-63122, Saint Genès Champanelle, France; Clermont Université, VetAgro Sup, UMR1213 Herbivores, BP 10448, F-63000, Clermont-Ferrand, France.

ABSTRACT

Background: Nutrition affects milk composition thus influencing its nutritional properties. Nutrition also modifies the expression of mammary genes, whose regulation is not fully understood. MicroRNAs (miRNA) are small non coding RNA which are important post-transcriptional regulators of gene expression by targeting messenger RNAs. Our goal was to characterize miRNA whose expression is regulated by nutrition in the lactating goat mammary gland, which may provide clues to deciphering regulations of the biosynthesis and secretion of milk components.

Methodology/principal findings: Using high-throughput sequencing technology, miRNomes of the lactating mammary gland were established from lactating goats fed ad libitum or deprived of food for 48 h affecting milk production and composition. High throughput miRNA sequencing revealed 30 miRNA with an expression potentially modulated by food deprivation; 16 were down-regulated and 14 were up-regulated. Diana-microT predictive tools suggested a potential role for several nutriregulated miRNA in lipid metabolism. Among the putative targets, 19 were previously identified as differently expressed genes (DEG). The functions of these 19 DEG revealed, notably, their involvement in tissue remodelling.

Conclusion/significance: In conclusion, this study offers the first evidence of nutriregulated miRNA in the ruminant mammary gland. Characterization of these 30 miRNA could contribute to a clearer understanding of gene regulation in the mammary gland in response to nutrition.

No MeSH data available.