DOI QR코드

DOI QR Code

miR-380-3p promotes β-casein expression by targeting αS1-casein in goat mammary epithelial cells

  • Ning Song (Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University) ;
  • Jun Luo (Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University) ;
  • Lian Huang (Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University) ;
  • Xiaoying Chen (Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University) ;
  • Huimin Niu (Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University) ;
  • Lu Zhu (Shaanxi Key Laboratory of Molecular Biology for Agriculture, College of Animal Science and Technology, Northwest A&F University)
  • Received : 2023.01.05
  • Accepted : 2023.03.28
  • Published : 2023.10.01

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.

Keywords

Acknowledgement

The authors are grateful for the support by National Natural Science Foundation of China (grant number 31772575), Transgenic New Species Breeding Program of China (grant number 2018ZX0800802B) and Innovation Support Plan of Shaanxi Province (grant number 2021TD-31).

References

  1. Hochwallner H, Schulmeister U, Swoboda I, et al. Infant milk formulas differ regarding their allergenic activity and induction of T-cell and cytokine responses. Allergy 2017;72:416-24. https://doi.org/10.1111/all.12992
  2. Hochwallner H, Schulmeister U, Swoboda I, Spitzauer S, Valenta R. Cow's milk allergy: From allergens to new forms of diagnosis, therapy and prevention. Methods 2014;66:22-33. https://doi.org/10.1016/j.ymeth.2013.08.005
  3. Caubet JC, Lin J, Ahrens B, et al. Natural tolerance development in cow's milk allergic children: IgE and IgG4 epitope binding. Allergy 2017;72:1677-85. https://doi.org/10.1111/all.13167
  4. Carillier-Jacquin C, Larroque H, Robert-Granie C. Including a(s1) casein gene information in genomic evaluations of French dairy goats. Genet Sel Evol 2016;48:54. https://doi.org/10.1186/s12711-016-0233-x
  5. Wang Q, Ren N, Cai Z, et al. Paraquat and MPTP induce neurodegeneration and alteration in the expression profile of microRNAs: the role of transcription factor Nrf2. NPJ Parkinsons Dis 2017;3:31. https://doi.org/10.1038/s41531-017-0033-1
  6. Li S, Wu D, Jia H, Zhang Z. Long non-coding RNA LRRC75AAS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC. Cell Death Dis 2020;11:643. https://doi.org/10.1038/s41419-020-02821-2
  7. Holliday H, Yang J, Dodson E, et al. miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma. Mol Ther 2022;30:1119-34. https://doi.org/10.1016/j.ymthe.2022.01.004
  8. Song N, Chen Y, Luo J, et al. Negative regulation of alpha(S1)-casein (CSN1S1) improves beta-casein content and reduces allergy potential in goat milk. J Dairy Sci 2020;103:9561-72. https://doi.org/10.3168/jds.2020-18595
  9. Kung MH, Lee YJ, Hsu JT, Huang MC, Ju YT. A functional study of proximal goat beta-casein promoter and intron 1 in immortalized goat mammary epithelial cells. J Dairy Sci 2015;98:3859-75. https://doi.org/10.3168/jds.2014-9054
  10. Wang W, Zang X, Liu Y, et al. Dynamic miRNA landscape links mammary gland development to the regulation of milk protein expression in mice. Animals 2022;12:727. https://doi.org/10.3390/ani12060727
  11. Cai W, Li C, Li J, Song J, Zhang S. Integrated small RNA sequencing, transcriptome and GWAS data reveal microRNA regulation in response to milk protein traits in Chinese Holstein cattle. Front Genet 2021;12:726706. https://doi.org/10.3389/fgene.2021.726706
  12. Cui Y, Sun X, Jin L, et al. MiR-139 suppresses beta-casein synthesis and proliferation in bovine mammary epithelial cells by targeting the GHR and IGF1R signaling pathways. BMC Vet Res 2017;13:350. https://doi.org/10.1186/s12917-017-1267-1
  13. Duman E, Ozmen O, Kul S. Oar-miR-16b and oar-miR-27a: negatively correlated with milk yield and milk protein in sheep. Anim Biotechnol 2022;33:1466-79. https://doi.org/10.1080/10495398.2021.1908317
  14. Zhang Y, Wu Q, Liu J, An X, Cao B. Circ-140/chi-miR-8516/STC1-MMP1 regulates alpha s1-/beta-casein secretion and lipid formation in goat mammary epithelial cells. Genes 2021;12:671. https://doi.org/10.3390/genes12050671
  15. Liu X, Du B, Zhang P, et al. miR-380-3p regulates melanogenesis by targeting SOX6 in melanocytes from alpacas (Vicugna pacos). BMC Genomics 2019;20:962. https://doi.org/10.1186/s12864-019-6343-4
  16. Li X, Lou X, Xu S, Du J, Wu J. Hypoxia inducible factor-1 (HIF-1 alpha) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723. Biol Res 2020;53:35. https://doi.org/10.1186/s40659-020-00302-6
  17. Luo R, Li L, Xiao F, Fu J. LncRNA FLG-AS1 mitigates diabetic retinopathy by regulating retinal epithelial cell inflammation, oxidative stress, and apoptosis via miR-380-3p/SOCS6 axis. Inflammation 2022;45:1936-49. https://doi.org/10.1007/s10753-022-01665-6
  18. Cai Z, Zheng F, Ding Y, et al. 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 2019;171:515-29. https://doi.org/10.1093/toxsci/kfz162
  19. Jiang Z, Song X, Wei Y, Li Y, Kong D, Sun J. N(6)-methyl-adenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer. Bioengineered 2022;13:14460-71. https://doi.org/10.1080/21655979.2022.2088497
  20. Kobayashi K, Omatsu N, Han L, Shan-Ni L, Nishimura T. Early effects of lipoteichoic acid from Staphylococcus aureus on milk production-related signaling pathways in mouse mammary epithelial cells. Exp Cell Res 2022;420:113352. https://doi.org/10.1016/j.yexcr.2022.113352
  21. Jabed A, Wagner S, McCracken J, Wells DN, Laible G. Targeted microRNA expression in dairy cattle directs production of beta-lactoglobulin-free, high-casein milk. Proc Natl Acad Sci USA 2012;109:16811-6. https://doi.org/10.1073/pnas.1210057109
  22. Laible G, Smolenski G, Wheeler T, Brophy B. Increased gene dosage for beta- and kappa-casein in transgenic cattle improves milk composition through complex effects. Sci Rep 2016;6:37607. https://doi.org/10.1038/srep37607
  23. Zhong W, Shen J, Liao X, et al. Camellia (Camellia oleifera Abel.) seed oil promotes milk fat and protein synthesis-related gene expression in bovine mammary epithelial cells. Food Sci Nutr 2020;8:419-27. https://doi.org/10.1002/fsn3.1326
  24. Morammazi S, Masoudi AA, Torshizi RV, Pakdel A. Differential expression of the Alpha S1 casein and Beta-lactoglobulin genes in different physiological stages of the Adani goats mammary glands. Iran J Biotechnol 2016;14:278-85. https://doi.org/10.15171/ijb.1171
  25. Reichenstein M, Rauner G, Barash T. 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 2011;78:585-96. https://doi.org/10.1002/mrd.21345
  26. Kobayashi K, Tsugami Y, Suzuki N, Suzuki T, Nishimura T. 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 2022;389:501-15. https://doi.org/10.1007/s00441-022-03651-8
  27. Liu X, Shen J, Zong J, Liu J, Jin Y. Beta-sitosterol promotes milk protein and fat syntheses-related genes in bovine mammary epithelial cells. Animals 2021;11:3238. https://doi.org/10.3390/ani11113238
  28. Tsugami Y, Wakasa H, Kawahara M, Nishimura T, Kobayashi K. Isoflavones and their metabolites influence the milk production ability of bovine mammary epithelial cells in a type-specific manner. J Anim Sci 2022;93:e13720. https://doi.org/10.1111/asj.13720
  29. Khan MZ, Khan A, Xiao J, et al. Role of the JAK-STAT pathway in bovine mastitis and milk production. Animals 2020;10:2107. https://doi.org/10.3390/ani10112107
  30. Ghosh A, Radhakrishnan R. Time-dependent antagonist-agonist switching in receptor tyrosine kinase-mediated signaling. BMC Bioinformatics 2019;20:242. https://doi.org/10.1186/s12859-019-2816-3