miR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3’-untranslated region (3’UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.
Abstract
Objective: αS1-Casein is more closely associated with milk allergic reaction than other milk protein components. microRNA (miRNA) is a class of small non-coding RNAs that modulate multiple biological progresses by the target gene. However, the post-transcriptional regulation of αS1-casein expression by miRNA in ruminants remains unclear. This study aims to explore the regulatory roles of miR-380-3p on αS1-casein synthesis in goat mammary epithelial cells (GMEC). Methods: αS1-Casein gene and miR-380-3p expression was measured in dairy goat mammary gland by quantitative real-time polymerase chain reaction (qRT-PCR). miR-380-3p overexpression and knockdown were performed by miR-380-3p mimic or inhibitor in GMEC. The effect of miR-380-3p on αS1-casein synthesis was detected by qRT-PCR, western blot, luciferase and chromatin immunoprecipitation assays in GMEC. Results: Compared with middle-lactation period, αS1-casein gene expression is increased, while miR-380-3p expression is decreased during peak-lactation of dairy goats. miR-380-3p reduces αS1-casein abundance by targeting the 3’-untranslated region (3’UTR) of αS1-casein mRNA in GMEC. miR-380-3p enhances β-casein expression and signal transducer and activator of transcription 5a (STAT5a) activity. Moreover, miR-380-3p promotes β-casein abundance through target gene αS1-casein, and activates β-casein transcription by enhancing the binding of STAT5 to β-casein gene promoter region. Conclusion: miR-380-3p decreases αS1-casein expression and increases β-casein expression by targeting αS1-casein in GMEC, which supplies a novel strategy for reducing milk allergic potential and building up milk quality in ruminants.
참고문헌 (30)
- Hochwallner H, "Infant milk formulas differ regarding their allergenic activity and induction of T-cell and cytokine responses", Allergy, 72, pp.416~424 (2017)[DOI]
- Hochwallner H, "Cow's milk allergy : From allergens to new forms of diagnosis, therapy and prevention", Methods, 66, pp.22~33 (2014)[DOI]
- Caubet JC, "Natural tolerance development in cow's milk allergic children : IgE and IgG4 epitope binding", Allergy, 72, pp.1677~1685 (2017)[DOI]
- Carillier-Jacquin C, "Including a(s1)casein gene information in genomic evaluations of French dairy goats", Genet Sel Evol, 48, pp.54~ (2016)[DOI]
- Wang Q, "Paraquat and MPTP induce neurodegeneration and alteration in the expression profile of microRNAs : the role of transcription factor Nrf2", NPJ Parkinsons Dis, 3, pp.31~ (2017)[DOI]
- Li S, "Long non-coding RNA LRRC75AAS1facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC", Cell Death Dis, 11, pp.643~ (2020)[DOI]
- Holliday H, "miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma", Mol Ther, 30, pp.1119~1134 (2022)[DOI]
- Song N, "Negative regulation of alpha(S1)-casein(CSN1S1)improves beta-casein content and reduces allergy potential in goat milk", J Dairy Sci, 103, pp.9561~9572 (2020)[DOI]
- Kung MH, "A functional study of proximal goat beta-casein promoter and intron 1in immortalized goat mammary epithelial cells", J Dairy Sci, 98, pp.3859~3875 (2015)[DOI]
- Wang W, "Dynamic miRNA landscape links mammary gland development to the regulation of milk protein expression in mice", Animals, 12, pp.727~ (2022)[DOI]
- Cai W, "Integrated small RNA sequencing, transcriptome and GWAS data reveal microRNA regulation in response to milk protein traits in Chinese Holstein cattle", Front Genet, 12, pp.726706~ (2021)[DOI]
- Cui Y, "MiR-139 suppresses beta-casein synthesis and proliferation in bovine mammary epithelial cells by targeting the GHR and IGF1R signaling pathways", BMC Vet Res, 13, pp.350~ (2017)[DOI]
- Duman E, "Oar-miR-16b and oar-miR-27a : negatively correlated with milk yield and milk protein in sheep", Anim Biotechnol, 33, pp.1466~1479 (2022)[DOI]
- Zhang Y, "Circ-140", chi-miR-8516, beta-casein secretion and lipid formation in goat mammary epithelial cells, pp.Genes, 2021[DOI]
- Liu X, "miR-380-3p regulates melanogenesis by targeting SOX6 in melanocytes from alpacas(Vicugna pacos)", BMC Genomics, 20, pp.962~ (2019)[DOI]
- Li X, "Hypoxia inducible factor-1(HIF-1 alpha)reduced inflammation in spinal cord injury via miR-380-3p", NLRP3 by Circ 0001723, 2020, pp.53, 35~
- Luo R, "LncRNA FLG-AS1 mitigates diabetic retinopathy by regulating retinal epithelial cell inflammation, oxidative stress, and apoptosis via miR-380-3p", SOCS6 axis, 2022, pp.45, 1936~1949
- Cai Z, "Nrf2-regulated miR-380-3p blocks the translation of Sp3 protein and its mediation of paraquat-induced toxicity in mouse neuroblastoma N2a cells", Toxicol Sci, 171, pp.515~529 (2019)[DOI]
- Jiang Z, "N(6)-methyladenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer", Bioengineered, 13, pp.14460~14471 (2022)[DOI]
- Kobayashi K, "Early effects of lipoteichoic acid from Staphylococcus aureus on milk production-related signaling pathways in mouse mammary epithelial cells", Exp Cell Res, 420, pp.113352~ (2022)[DOI]
- Jabed A, "Targeted microRNA expression in dairy cattle directs production of beta-lactoglobulin-free, high-casein milk", Proc Natl Acad Sci USA, 109, pp.16811~16816 (2012)[DOI]
- Laible G, "Increased gene dosage for beta-and kappa-casein in transgenic cattle improves milk composition through complex effects", Sci Rep, 6, pp.37607~ (2016)[DOI]
- Zhong W, "Camellia(Camellia oleifera Abel. )seed oil promotes milk fat and protein synthesisrelated gene expression in bovine mammary epithelial cells", Food Sci Nutr, 8, pp.419~427 (2020)[DOI]
- Morammazi S, "Differential expression of the Alpha S1 casein and Beta-lactoglobulin genes in different physiological stages of the Adani goats mammary glands", Iran J Biotechnol, 14, pp.278~285 (2016)[DOI]
- Reichenstein M, "Conditional repression of STAT5 expression during lactation reveals its exclusive roles in mammary gland morphology, milk-protein gene expression, and neonate growth", Mol Reprod Dev, 78, pp.585~596 (2011)[DOI]
- Kobayashi K, "Lactose on the basolateral side of mammary epithelial cells inhibits milk production concomitantly with signal transducer and activator of transcription 5 inactivation", Cell Tissue Res, 389, pp.501~515 (2022)[DOI]
- Liu X, "Beta-sitosterol promotes milk protein and fat syntheses-related genes in bovine mammary epithelial cells", Animals, 11, pp.3238~ (2021)[DOI]
- Tsugami Y, "Isoflavones and their metabolites influence the milk production ability of bovine mammary epithelial cells in a type-specific manner", J Anim Sci, 93, pp.e13720~ (2022)[DOI]
- Khan MZ, "Role of the JAK-STAT pathway in bovine mastitis and milk production", Animals, 10, pp.2107~ (2020)[DOI]
- Ghosh A, "Time-dependent antagonistagonist switching in receptor tyrosine kinase-mediated signaling", BMC Bioinformatics, 20, pp.242~ (2019)[DOI]