Cząsteczki mikroRNA – nowy biologicznie aktywny składnik mleka kobiecego*
Patrycja Jakubek 1 , Joanna Cieślewicz 1 , Agnieszka Bartoszek 1Abstrakt
Cząsteczki mikroRNA są krótkimi, niekodującymi oligonukleotydami odpowiadającymi za potranskrypcyjną regulację ekspresji genów. W wyniku ich aktywności kontrolowanych jest wiele procesów komórkowych oraz szlaków sygnalizacyjnych. Od 2010 roku wiadomo, że wchodzą one w skład mleka kobiecego, które obecnie uznaje się za jedno z najbogatszych pokarmowych źródeł mikroRNA. Funkcje tych cząsteczek w organizmie karmionego mlekiem matki dziecka są związane z kształtowaniem się układu odpornościowego, wzrostem i prawidłowym rozwojem. Wykazano, że cząsteczki mikroRNA pochodzące z mleka kobiecego są stabilne w warunkach in vitro symulujących trawienie w przewodzie pokarmowym niemowlęcia oraz mogą podlegać wchłanianiu przez enterocyty, przez co stanowią potencjalnie bioaktywny składnik mleka kobiecego sprzyjający rozwojowi niemowląt karmionych piersią. Ochronę przed degradacją w wyniku działania RNaz bądź niskiego pH zapewnia otoczka egzosomów, które stanowią nośnik mikroRNA we frakcji odtłuszczonej mleka, natomiast we frakcji lipidowej i komórkowej funkcję tę przypisuje się koloidalnym skupiskom pęcherzyków, zwanych kuleczkami tłuszczowymi, oraz laktocytom. W przeciwieństwie do mleka matki, sztuczne mieszanki mlekozastępcze zawierają tylko nieliczne cząsteczki mikroRNA – co więcej – wywodzące się od innych organizmów. Można przypuszczać, że dodatek krótkich RNA o sekwencjach identycznych z mikroRNA występującymi naturalnie w mleku kobiecym do preparatów do karmienia zastępczego niemowląt może stać się nowym, ważnym składnikiem mieszanek mlekozastępczych.
Przypisy
- 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