MicroRNAs as novel bioactive components of human breastmilk

REVIEW ARTICLE

MicroRNAs as novel bioactive components of human breastmilk

Patrycja Jakubek 1 , Joanna Cieślewicz 1 , Agnieszka Bartoszek 1

1. Katedra Chemii, Technologii i Biotechnologii Żywności, Wydział Chemiczny, Politechnika Gdańska, Gdańsk,

Published: 2020-05-15
DOI: 10.5604/01.3001.0014.1434
GICID: 01.3001.0014.1434
Available language versions: en pl
Issue: Postepy Hig Med Dosw 2020; 74 : 103-115

 

Abstract

MicroRNAs are short, non-coding oligonucleotides that regulate gene expression at the post-transcriptional level. These small molecules participate in the control of various cellular processes and signalling pathways. Since 2010 microRNAs have been recognized as a new bioactive component of breastmilk, which is an exceptionally rich source of these oligonucleotides. In infants fed with breastmilk, microRNAs are involved in the growth and proper development as well as maturation of the immune system. It has been demonstrated that microRNAs are resistant to harsh conditions during in vitro digestion in simulated gastrointestinal tract of a newborn and, therefore, may be absorbed by the intestinal cells. Protection against RNase activity and low pH is provided by exosomes, which are carriers of microRNAs in skim milk or by fat globules and milk cells. It has been reported that, in contrast to human milk, infant formulas contain only a few microRNAs, which have been derived from other organisms, such as cow or soy. It may be presumed that supplementing infant formulas with microRNAs identical with those which occur naturally in breastmilk may constitute a new way of designing artificial substitutes for human breastmilk.

References

  • 1. Alsaweed M., Hartmann P.E., Geddes D.T., Kakulas F.: MicroRNAsin breastmilk and the lactating breast: Potential immunoprotectorsand developmental regulators for the infant and the mother. Int. J.Environ. Res. Public Health, 2015; 12: 13981–14020 2 Alsaweed M., Hepworth A.R., Lefèvre C., Hartmann P.E., GeddesD.T., Hassiotou F.: Human milk microRNA and total RNA differdepending on milk fractionation. J. Cell. Biochem., 2015; 116:2397–2407
    Google Scholar
  • 2. cells and rat small intestinal IEC–6 cells. J. Nutr., 2015; 145: 2201–2206
    Google Scholar
  • 3. Alsaweed M., Lai C.T., Hartmann P.E., Geddes D.T., Kakulas F.:Human milk cells and lipids conserve numerous known and novelmiRNAs, some of which are differentially expressed during lactation.PLoS One, 2016; 11: e0152610
    Google Scholar
  • 4. Alsaweed M., Lai C.T., Hartmann P.E., Geddes D.T., Kakulas F.: Humanmilk cells contain numerous miRNAs that may change withmilk removal and regulate multiple physiological processes. Int. J.Mol. Sci., 2016; 17: 956
    Google Scholar
  • 5. Alsaweed M., Lai C.T., Hartmann P.E., Geddes D.T., Kakulas F.: Humanmilk miRNAs primarily originate from the mammary gland resultingin unique miRNA profiles of fractionated milk. Sci. Rep., 2016; 6: 20680
    Google Scholar
  • 6. Baier S.R., Nguyen C., Xie F., Wood J.R., Zempleni J.: MicroRNAsare absorbed in biologically meaningful amounts from nutritionallyrelevant doses of cow milk and affect gene expression in peripheralblood mononuclear cells, HEK-293 kidney cell cultures, and mouselivers. J. Nutr., 2014; 144: 1495–1500
    Google Scholar
  • 7. Barh D., Malhotra R., Ravi B., Sindhurani P.: MicroRNA let-7: Anemerging next-generation cancer therapeutic. Curr. Oncol., 2010;17: 70–80 8 Carney M.C., Tarasiuk A., DiAngelo S.L., Silveyra P., Podany A.,Birch L.L., Paul I.M., Kelleher S., Hicks S.D.: Metabolism-related microRNAsin maternal breast milk are influenced by premature delivery.Pediatr. Res., 2017; 82: 226–236
    Google Scholar
  • 8. Mediators Inflammation, 2015; 2015: 629862
    Google Scholar
  • 9. Catassi C., Bonucci A., Coppa G.V., Carlucci A., Giorgi P.L.: Intestinalpermeability changes during the first month: effect of natural versusartificial feeding. J. Pediatr. Gastroenterol. Nutr., 1995; 21: 383–386
    Google Scholar
  • 10. Chan S.Y., Snow J.W.: Formidable challenges to the notion ofbiologically important roles for dietary small RNAs in ingestingmammals. Genes Nutr., 2017; 12: 13
    Google Scholar
  • 11. Chaszczewska-Markowska M., Sagan M., Bogunia-Kubik K.:Układ renina-angiotensyna-aldosteron (RAA) – fizjologia i molekularnemechanizmy funkcjonowania. Postępy Hig. Med. Dośw.,2016; 70: 917–927
    Google Scholar
  • 12. Chen X., Gao C., Li H., Huang L., Sun Q., Dong Y., Tian C., Gao S.,Dong H., Guan D., Hu X., Zhao S., Li L., Zhu L., Yan Q. i wsp.: Identificationand characterization of microRNAs in raw milk during differentperiods of lactation, commercial fluid, and powdered milkproducts. Cell Res., 2010; 20: 1128–1137
    Google Scholar
  • 13. Chen Z., Luo J., Sun S., Cao D., Shi H., Loor J.J.: miR-148a and miR-17-5p synergistically regulate milk TAG synthesis via PPARGC1A andPPARA in goat mammary epithelial cells. RNA Biol., 2017; 14: 326–338
    Google Scholar
  • 14. Cochrane D.R., Spoelstra N.S., Richer J.K.: The role of miRNAs inprogesterone action. Mol. Cell. Endocrinol., 2012; 357: 50–59
    Google Scholar
  • 15. De Candia P., De Rosa V., Casiraghi M., Matarese G.: ExtracellularRNAs: A secret arm of immune system regulation. J. Biol. Chem.,2016; 291: 7221–7228
    Google Scholar
  • 16. Do D.N., Dudemaine P.L., Li R., Ibeagha-Awemu E.M.: Co-expressionnetwork and pathway analyses reveal important modulesof miRNAs regulating milk yield and component traits. Int. J. Mol.Sci., 2017; 18: 1560
    Google Scholar
  • 17. Do D.N., Li R., Dudemaine P.L., Ibeagha-Awemu E.M.: MicroRNAroles in signalling during lactation: an insight from differential expression,time course and pathway analyses of deep sequence data.Sci. Rep., 2017; 7: 44605
    Google Scholar
  • 18. Duursma A.M., Kedde M., Schrier M., le Sage C., Agami R.: miR-148targets human DNMT3b protein coding region. RNA, 2008; 14: 872–877
    Google Scholar
  • 19. Dziedzic M., Orłowska E., Powrózek T., Solski J.: Role of circulatingmicroRNA in hemodialyzed patients. Postępy Hig. Med. Dośw.,2016; 70: 1362–1366
    Google Scholar
  • 20. Escrevente C., Keller S., Altevogt P., Costa J.: Interaction and uptakeof exosomes by ovarian cancer cells. BMC Cancer, 2011; 11: 108
    Google Scholar
  • 21. Estève P.O., Chin H.G., Pradhan S.: Human maintenance DNA(cytosine-5)-methyltransferase and p53 modulate expression of p53-repressed promoters. Proc. Natl. Acad. Sci. USA, 2005; 102: 1000–1005
    Google Scholar
  • 22. Fernández-Hernando C., Suárez Y., Rayner K.J., Moore K.J.: MicroRNAsin lipid metabolism. Curr. Opin. Lipidol., 2011; 22: 86–92
    Google Scholar
  • 23. Ferraro L., Ravo M., Nassa G., Tarallo R., De Filippo M.R., GiuratoG., Cirillo F., Stellato C., Silvestro S., Cantarella C., Rizzo F., CiminoD., Friard O., Biglia N., De Bortoli M. i wsp.: Effects of oestrogen onmicroRNA expression in hormone-responsive breast cancer cells.Horm. Cancer., 2012; 3: 65–78
    Google Scholar
  • 24. Floris I., Kraft J.D., Altosaar I.: Roles of microRNA across prenataland postnatal periods. Int. J. Mol. Sci, 2016; 17: 1994
    Google Scholar
  • 25. Flöter J., Kaymak I., Schulze A.: Regulation of metabolic activityby p53. Metabolites, 2017; 7: 21
    Google Scholar
  • 26. Friedman R.C., Farh K.K., Burge C.B., Bartel D.P.: Most mammalianmRNAs are conserved targets of microRNAs. Genome Res.,2009; 19: 92–105
    Google Scholar
  • 27. Golan-Gerstl R., Shiff Y.E., Moshayoff V., Schecter D., LeshkowitzD., Reif S.: Characterization and biological function of milk-derivedmiRNAs. Mol. Nutr. Food Res., 2017; 61: 1700009
    Google Scholar
  • 28. Gonzalez-Martin A., Adams B.D., Lai M., Shepherd J., Salvador-Bernaldez M., Salvador J.M., Lu J., Nemazee D., Xiao C.: The microRNAmiR-148a functions as a critical regulator of B cell tolerance andautoimmunity. Nat. Immunol., 2016; 17: 433–440
    Google Scholar
  • 29. Goossens G.H.: The renin-angiotensin system in the pathophysiologyof type 2 diabetes. Obes. Facts, 2012; 5: 611–624
    Google Scholar
  • 30. Grasso M., Piscopo P., Crestini A., Confaloni A., Denti M.A.: CirculatingmicroRNAs in neurodegenerative diseases. Exp. Suppl.,2015; 106: 151–169
    Google Scholar
  • 31. Grenda A., Budzyński M., Filp A.A.: Biogeneza cząsteczek mikroRNAoraz ich znaczenie w powstawaniu i przebiegu wybranych zaburzeńhematologicznych. Postępy Hig. Med. Dośw., 2013; 67: 174–185
    Google Scholar
  • 32. Gu Y., Li M., Wang T., Liang Y., Zhong Z., Wang X. Zhou Q., ChenL., Lang Q., He Z., Chen X., Gong J., Gao X., Li X., Lv X.: Lactation-relatedmicroRNA expression profiles of porcine breast milk exosomes.PLoS One, 2012; 7: e43691
    Google Scholar
  • 33. Hallberg L., Rossander-Hultén L., Brune M., Gleerup A.: Bioavailabilityin man of iron in human milk and cow’s milk in relation totheir calcium contents. Pediatr. Res., 1992; 31: 524–527
    Google Scholar
  • 34. Hassiotou F., Beltran A., Chetwynd E., Stuebe A.M., Twigger A.J.,Metzger P., Trengove N., Lai C.T., Filgueira L., Blancafort P., HartmannP.E.: Breastmilk is a novel source of stem cells with multilineage differentiationpotential. Stem Cells, 2012; 30: 2164–2174
    Google Scholar
  • 35. Hassiotou F., Geddes D.T.: Immune cell-mediated protectionof the mammary gland and the infant during breastfeeding. Adv.Nutr., 2015; 6: 267–275
    Google Scholar
  • 36. Hassiotou F., Hepworth A.R., Beltran A.S., Mathews M.M., StuebeA.M., Hartmann P.E., Filgueira L., Blancafort P.: Expression of thepluripotency transcription factor OCT4 in the normal and aberrantmammary gland. Front. Oncol., 2013; 3: 79
    Google Scholar
  • 37. Hassiotou F., Hepworth A.R., Metzger P., Lai C.T., Trengove N., HartmannP.E., Filgueira L.: Maternal and infant infections stimulate a rapidleukocyte response in breastmilk. Clin. Transl. Immunol., 2013; 2: e3
    Google Scholar
  • 38. Hassiotou F., Hepworth A.R., Williams T.M., Twigger A.J., PerrellaS., Lai C.T., Filgueira L., Geddes D.T., Hartmann P.E.: Breastmilkcell and fat contents respond similarly to removal of breastmilk bythe infant. PLoS One, 2013; 8: e78232
    Google Scholar
  • 39. Hassiotou F., Mobley A., Geddes D., Hartmann P., Wilkie T.:Breastmilk imparts the mother’s stem cells to the infant. FASEB J.,2015; 29: 876–878
    Google Scholar
  • 40. Hermann A., Goyal R., Jeltsch A.: The Dnmt1 DNA-(cytosine-C5)-methyltransferase methylates DNA processively with high preferencefor hemimethylated target sites. J. Biol. Chem., 2004; 279:48350–48359
    Google Scholar
  • 41. Herrington J., Carter-Su C.: Signaling pathways activated by thegrowth hormone receptor. Trends Endocrinol. Metab., 2001; 12: 252–257
    Google Scholar
  • 42. Hill P.D., Aldag J.C., Demirtas H., Naeem V., Parker N.P., ZinamanM.J., Chatterton R.T. Jr.: Association of serum prolactin and oxytocinwith milk production in mothers of preterm and term infants. Biol.Res. Nurs., 2009; 10: 340–349
    Google Scholar
  • 43. Hoddinott P., Tappin D., Wright C.: Breast feeding. BMJ, 2008;336: 881–887
    Google Scholar
  • 44. Hoh J., Jin S., Parrado T., Edington J., Levine A.J., Ott J.: Thep53MH algorithm and its application in detecting p53-responsivegenes. Proc. Natl. Acad. Sci. USA, 2002; 99: 8467–8472
    Google Scholar
  • 45. Hong Z., Hong H., Liu J., Zheng X., Huang M., Li C., Xia J.: miR-106a is downregulated in peripheral blood mononuclear cells ofchronic hepatitis B and associated with enhanced levels of interleukin-
    Google Scholar
  • 46. Howard K.M., Kusuma R.J., Baier S.R., Friemel T., Markham L.,Vanamala J., Zempleni J.: Loss of miRNAs during processing and storageof cow’s (Bos taurus) milk. J. Agric. Food Chem., 2015; 63: 588–592
    Google Scholar
  • 47. Huang H.C., Yu H.R., Huang L.T., Huang H.C., Chen R.F., Lin I.C.,Ou C.Y., Hsu T.Y., Yang K.D.: miRNA-125b regulates TNF-α productionin CD14+ neonatal monocytes via post-transcriptional regulation. J.Leukoc. Biol., 2012; 92: 171–182
    Google Scholar
  • 48. Imoto I., Pimkhaokham A., Watanabe T., Saito-Ohara F., SoedaE., Inazawa J.: Amplification and overexpression of TGIF2, a novelhomeobox gene of the TALE superclass, in ovarian cancer cell lines.Biochem. Biophys. Res. Commun., 2000; 276: 264–270
    Google Scholar
  • 49. Kahn S., Liao Y., Du X., Xu W., Li J., Lönnerdal B.: Exosomal microRNAsin milk from mothers delivering preterm infants survivein vitro digestion and are taken up by human intestinal cells. Mol.Nutr. Food Res., 2018; 62: 1701050
    Google Scholar
  • 50. Kosaka N., Izumi H., Sekine K., Ochiya T.: MicroRNA as a newimmune-regulatory agent in breast milk. Silence, 2010; 1: 7
    Google Scholar
  • 51. Kozomara A., Griffiths-Jones S.: miRBase: Annotating high confidencemicroRNAs using deep sequencing data. Nucleic Acids Res.,2014; 42: D68–D73
    Google Scholar
  • 52. Kramer M.S.: “Breast is best”: The evidence. Early Hum. Dev.,2010; 86: 729–732
    Google Scholar
  • 53. Kramer M.S., Kakuma R.: Optimal duration of exclusive breastfeeding.Cochrane Database Syst. Rev., 2012; 2012: CD003517
    Google Scholar
  • 54. Kulski J.K., Hartmann P.E.: Milk insulin GH and TSH: Relationshipto changes in milk lactose, glucose and protein during lactogenesisin women. Endocrinol. Exp., 1983; 17: 317–326
    Google Scholar
  • 55. Kunz C., Rudloff S., Baier W., Klein N., Strobel S.: Oligosacchariesin human milk: Structural, functional, and metabolic aspects. Annu.Rev. Nutr., 2000; 20: 699–722
    Google Scholar
  • 56. Laskowska J., Książyk J.: Aktualne wytyczne dotyczące karmieniapiersią. Pediatr. Med. Rodz., 2011; 7: 110–114
    Google Scholar
  • 57. Le M.T., Teh C., Shyh-Chang N., Xie H., Zhou B., Korzh V., LodishH.F., Lim B.: MicroRNA-125b is a novel negative regulator of p53.Genes Dev., 2009; 23: 862–876
    Google Scholar
  • 58. Le Huërou-Luron I., Blat S., Boudry G.: Breast- v. formula-feeding:impacts on the digestive tract and immediate and long-term healtheffects. Nutr. Res. Rev., 2010; 23: 23–36
    Google Scholar
  • 59. Lemons J.A., Moye L., Hall D., Simmons M.: Differences in thecomposition of preterm and term human milk during early lactation.Pediatr. Res., 1982; 16: 113–117
    Google Scholar
  • 60. Li J., Chen L., Tang Q., Wu W., Gu H., Liu L., Wu J., Jiang H., DingH., Xia Y., Chen D., Hu Y., Wang X.: The role, mechanism and potentiallynovel biomarker of microRNA-17-92 cluster in macrosomia.Sci. Rep., 2015; 5: 17212
    Google Scholar
  • 61. Li J., Song Y., Wang Y., Luo J., Yu W.: MicroRNA-148a suppressesepithelial-to-mesenchymal transition by targeting ROCK1 in nonsmallcell lung cancer cells. Mol. Cell. Biochem., 2013; 380: 277–282
    Google Scholar
  • 62. Li R., Dudemaine P.L., Zhao X., Lei C., Ibeagha-Awemu E.M.:Comparative analysis of the miRNome of bovine milk fat, whey andcells. PLoS One, 2016; 11: e0154129
    Google Scholar
  • 63. Liao Y., Du X., Li J., Lönnerdal B.: Human milk exosomes and theirmicroRNAs survive digestion in vitro and are taken up by humanintestinal cells. Mol. Nutr. Food Res., 2017; 61: 1700082
    Google Scholar
  • 64. Lu Y., Li Z., Xie B., Song Y., Ye X., Liu P.: hsa-miR-20-5p attenuatesallergic inflammation in HMC-1 cells by targeting HDAC4. Mol.Immunol., 2019; 107: 84–90
    Google Scholar
  • 65. MacFarlane L.A., Murphy P.R.: MicroRNA: Biogenesis, functionand role in cancer. Curr. Genomics, 2010; 11: 537–561
    Google Scholar
  • 66. Malkaram S.A., Hassan Y.I., Zempleni J.: Online tools for bioinformaticsanalyses in nutrition sciences. Adv. Nutr., 2012; 3: 654–665
    Google Scholar
  • 67. Mathivanan S., Ji H., Simpson R.J.: Exosomes: Extracellular organellesimportant in intercellular communication. J. Proteomics,2010; 73: 1907–1920
    Google Scholar
  • 68. Melnik B.C., Schmitz G.: MicroRNAs: Milk’s epigenetic regulators.Best Pract. Res. Clin. Endocrinol. Metab., 2017; 31: 427–442
    Google Scholar
  • 69. Meunier L., Siddeek B., Vega A., Lakhdari N., Inoubli L., BellonR.P., Lemaire G., Mauduit C., Benahmed M.: Perinatal programmingof adult rat germ cell death after exposure to xenoestrogens: roleof microRNA miR-29 family in the down-regulation of DNA methyltransferasesand Mc1-1. Endocrinology, 2012; 153: 1936–1947
    Google Scholar
  • 70. Mishra P.J., Merlino G.: MicroRNA reexpression as differentiationtherapy in cancer. J. CIin. Invest., 2009; 119: 2119–2123
    Google Scholar
  • 71. Morera Pons S., Castellote Bargallo A.I., López Sabater M.C.:Analysis of human milk triacylglycerols by high-performance liquidchromatography with light-scattering detection. J. Chromatogr.A, 1998; 823: 475–482
    Google Scholar
  • 72. Munch E.M., Harris R.A., Mohammad M., Benham A.L., PejerreyS.M., Showalter L., Hu M., Shope C.D., Maningat P.D., Gunaratne P.H.,Haymond M., Aagaard K.: Transcriptome profiling of microRNA bynext-gen deep sequencing reveals known and novel miRNA speciesin the lipid fraction of human breast milk. PLoS One, 2013; 8: e50564
    Google Scholar
  • 73. Na R.S., E G.X., Sun W., Sun X.W., Qiu X.Y., Chen L.P., Huang Y.F.:Expressional analysis of immune-related miRNAs in breast milk.Genet. Mol. Res., 2015; 14: 11371–11376
    Google Scholar
  • 74. Neville M.C., McFadden T.B., Forsyth I.: Hormonal regulationof mammary differentiation and milk secretion. J. Mammary GlandBiol. Neoplasia, 2002; 7: 49–66
    Google Scholar
  • 75. O’Day E., Lal A.: MicroRNAs and their target gene networks inbreast cancer. Breast Cancer Res., 2010; 12: 201
    Google Scholar
  • 76. Pauley K.M., Cha S., Chan E.K.: MicroRNA in autoimmunity andautoimmune diseases. J. Autoimmun., 2009; 32: 189–194
    Google Scholar
  • 77. Perri M., Lucente M., Cannataro R., De Luca I.F., Gallelli L., MoroG., De Sarro G., Caroleo M.C., Cione E.: Variation in immune-relatedmicroRNAs profile in human milk amongst lactating women. MicroRNA,2018; 7: 107–114
    Google Scholar
  • 78. Perry B., Wang Y.: Appetite regulation and weight control: therole of gut hormones. Nutr. Diabetes, 2012; 2: e26
    Google Scholar
  • 79. Rani P., Vashisht M., Golla N., Shandilya S., Onteru S.K., SinghD.: Milk miRNAs encapsulated in exosomes are stable to human digestionand permeable to intestinal barrier in vitro. J. Funct. Foods,2017; 34: 431–439
    Google Scholar
  • 80. Reinhart B.J., Slack F.J., Basson M., Pasquinelli A.E., BettingerJ.C., Rougvie A.E., Horvitz H.R., Ruvkun G.: The 21-nucleotide let-7RNA regulates developmental timing in Ceanorhabditis elegans. Nature,2000; 403: 901–906
    Google Scholar
  • 81. Roush S., Slack F.J.: The let-7 family of microRNAs. Trends CellBiol., 2008; 18: 505–516
    Google Scholar
  • 82. Satoh J.I., Tabunoki H.: Comprehensive analysis of human microRNAtarget networks. BioData Min., 2011; 4: 17
    Google Scholar
  • 83. Schulte C., Zeller T.: MicroRNA-based diagnostics and therapyin cardiovascular disease – summing up the facts. Cardiovasc. Diagn.Ther., 2015; 5: 17–36
    Google Scholar
  • 84. Shandilya S., Rani P., Onteru S.K., Singh D.: Small interferingRNA in milk exosomes is resistant to digestion and cross intestinalbarrier in vitro. J. Agric. Food Chem., 2017; 65: 9506–9513
    Google Scholar
  • 85. Sikora E., Ptak W., Bryniarski K.: Immunoregulacja poprzez interferencyjnyRNA – mechanizmy, rola, perspektywy. Postępy Hig.Med. Dośw., 2011; 65: 482–495
    Google Scholar
  • 86. Takagi S., Nakajima M., Mohri T., Yokoi T.: Post-transcriptionalregulation of human pregnane X receptor by microRNA affectsthe expression of cytochrome P450 3A4. J. Biol. Chem., 2008; 283:9674–9680
    Google Scholar
  • 87. Takeuchi K., Reue K.: Biochemistry, physiology, and geneticsof GPAT, AGPAT, and lipid enzymes in triglyceride synthesis. Am. J.Physiol. Endocrinol. Metab., 2009; 296: E1195–E1209
    Google Scholar
  • 88. Title A.C., Denzler R., Stoffel M.: Uptake and function studiesof maternal milk-derived microRNAs. J. Biol. Chem., 2015; 290:23680–23691
    Google Scholar
  • 89. Vaishya S., Sarwade R.D., Seshadri V.: MicroRNA, proteins, andmetabolites as novel biomarkers for prediabetes, diabetes, and relatedcomplications. Front. Endocrinol., 2018; 9: 180
    Google Scholar
  • 90. Wagschal A., Najafi-Shoushtari S.H., Wang L., Geodeke L., SinhaS., deLemos A.S., Black J.C., Ramírez C.M., Li Y., Tewhey R., HatoumI., Shah N., Lu Y., Kristo F., Psychogios N. i wsp.: Genome-wide identificationof microRNAs regulating cholesterol and triglyceride homeostasis.Nat. Med., 2015; 21: 1290–1297
    Google Scholar
  • 91. Wang X.X., Zhang R., Li Y.: Expression of the miR-148/152 familyin acute myeloid leukemia and its clinical significance. Med. Sci.Monit., 2017; 23: 4768–4778
    Google Scholar
  • 92. Wang X.Y., Chen X.Y., Li J., Zhang H.Y., Liu J., Sun L.D.: miR-200aexpression in CD4+ T cells correlates with the expression of Th17/Treg cells and relevant cytokines in psoriasis vulgaris: A case controlstudy. Biomed. Pharmacother., 2017; 93: 1158–1164
    Google Scholar
  • 93. Wang Y.D., Wood W.I.: Amino acids of the human growth hormonereceptor that are required for proliferation and Jak–STATsignalling. Mol. Endocrinol., 1995; 9: 303–311
    Google Scholar
  • 94. Weber J.A., Baxter D.H., Zhang S., Huang D.Y., Huang K.H., LeeM.J., Galas D.J., Wang K.: The microRNA spectrum in 12 body fluids.Clin. Chem., 2010; 56: 1733–1741
    Google Scholar
  • 95. Wolf T., Baier S.R., Zempleni J.: The intestinal transport of bovine milkexosomes is mediated by endocytosis in human colon carcinoma Caco-
    Google Scholar
  • 96. Xiao C., Srinivasan L., Calado D.P., Patterson H.C., Zhang B., WangJ., Henderson J.M., Kutok J.L., Rajewsky K.: Lymphoproliferative diseaseand autoimmunity in mice with increased miR-17-92 expressionin lymphocytes. Nat. Immunol., 2008; 9: 405–414
    Google Scholar
  • 97. Yu J., Li Q., Xu Q., Liu L., Jiang B.: miR-148a inhibits angiogenesisby targeting ERBB3. J. Biomed. Res., 2011; 25: 170–177
    Google Scholar
  • 98. Zhang G., Estève P.O., Chin H.G., Terragni J., Dai N., Corrêa I.R.Jr., Pradhan S.: Small RNA-mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation. Nucleic AcidsRes., 2015; 43: 6112–6124
    Google Scholar
  • 99. Zhou B.P., Liao Y., Xia W., Zou Y., Spohn B., Hung M.C.: HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation.Nat. Cell. Biol., 2001; 3: 973–982
    Google Scholar
  • 100. Zhou Q., Li M., Wang X., Li Q., Wang T., Zhu Q., Zhou X., WangX., Gao X., Li X.: Immune-related microRNAs are abundant in breastmilk exosomes. Int. J. Biol. Sci., 2012; 8: 118–123
    Google Scholar
  • 101. Zwart W., Theodorou V., Carroll J.S.: Estrogen receptor-positivebreast cancer: A multidisciplinary challenge. Wiley Interdiscip. Rev.Syst. Biol. Med., 2011; 3: 216–230
    Google Scholar

Full text

Skip to content