Medical academic journalMedical academic journalМедицинский академический журнал1608-41012687-1378Eco-Vector6410610.17816/MAJ64106Analytical reviewsАналитические обзорыReview ArticleThe influence of lactoferrin on the epigenetic characteristics of mammalian cells of different typesВлияние лактоферрина на эпигенетические характеристики клеток млекопитающих разного типаhttps://orcid.org/0000-0003-0926-0549SharroufKinda AliШарруфКинда Али
Russian Federation

Master’s student, Department of Genetics and Biotechnology, Faculty of Biology and Soil

студентка 2-го курса магистратуры, кафедра генетики и биотехнологии, биолого-почвенный факультет

kinda996@yahoo.comhttps://orcid.org/0000-0003-2127-04596602838276H-4484-20144155-7314SuchkovaIrina O.СучковаИрина Олеговна
Russian Federation

MD, PhD (Biology), Senior Researcher, Laboratory of Molecular Cytogenetics of Mammalian Development, Department of Molecular Genetics

канд. биол. наук, старший научный сотрудник, лаборатория молекулярной цитогенетики развития млекопитающих, отдел молекулярной генетики

irsuchkova@mail.ruInstitute of Experimental MedicineФедеральное государственное бюджетное научное учреждение «Институт экспериментальной медицины»Saint Petersburg UniversityФедеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный университет»290320211006202121185952603202129032021Copyright ©; 2021, Sharrouf K.A., Suchkova I.O.Copyright ©; 2021, Шарруф К.А., Сучкова И.О.2021Sharrouf K.A., Suchkova I.O.Шарруф К.А., Сучкова И.О.https://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/MAJ/article/view/64106

Despite the huge amount of accumulated data, the study of the main mechanisms of interaction between proteins and epigenetic mechanisms in health and various pathologies remains one of the most important problems of molecular biology. The search for various endogenous and exogenous factors affecting the epigenome of eukaryotes continues to be relevant. Lactoferrin is the second most abundant milk protein and has proven to be a very promising anti-inflammatory, antifungal, antibacterial, and anti-cancer agent. This protein can act as a transcription factor regulating the expression of some genes. However, little attention has been paid to the use of lactoferrin as an epigenetic modulating factor. This review demonstrates that lactoferrin can directly and/or indirectly influence epigenetic mechanisms (DNA methylation, histone modification, chromatin compaction, and microRNA pathways) in different types of cells, in particular cancer cells.

Несмотря на огромное количество накопленных данных, изучение особенностей взаимодействия между белками и эпигенетическими механизмами в норме и при различных патологиях остается одной из важнейших задач молекулярной биологии. Поиск эндогенных и экзогенных факторов, влияющих на эпигеном эукариот, по-прежнему актуален. Лактоферрин является вторым по распространенности белком молока, который обладает противовоспалительными, противогрибковыми, антибактериальными и противораковыми свойствами. Этот белок может действовать как фактор транскрипции, регулирующий экспрессию некоторых генов. Однако мало внимания уделяется использованию лактоферрина в качестве фактора, модулирующего эпигенетические модификации (механизмы). В данном обзоре представлены данные, указывающие на то, что лактоферрин может прямо и/или косвенно влиять на эпигенетические механизмы (метилирование ДНК, модификация гистонов, компактизация хроматина и микроРНК-пути) в различных типах клеток, в частности в опухолевых клетках.

lactoferrinDNA methylationmiRNAchromatinepigeneticsepi-miRNATET enzymesERHIFлактоферринметилирование ДНКмиРНКхроматинэпигенетикаэпи-миРНКТЕТ-ферментырецепторы эстрогенафакторы, индуцируемые гипоксиейThis work was carried out in the framework of the state task of the Russian Academy of Sciences (RAN).McGee SL, Hargreaves M. Epigenetics and exercise. Trends Endocrinol Metab. 2019;30(9):636–645. DOI: 10.1016/j.tem.2019.06.002McGee S.L., Hargreaves M. Epigenetics and exercise // Trends Endocrinol. Metab. 2019. Vol. 30, No. 9. P. 636–645. DOI: 10.1016/j.tem.2019.06.002Bird AP, Wolffe AP. Methylation-induced repression — belts, braces, and chromatin. Cell. 1999;99(5):451–454. DOI: 10.1016/s0092-8674(00)81532-9Bird A.P., Wolffe A.P. Methylation-induced repression--belts, braces, and chromatin // Cell. 1999. Vol. 99, No. 5. P. 451–454. DOI: 10.1016/s0092-8674(00)81532-9Ramassone A, Pagotto S, Veronese A, Visone R. Epigenetics and MicroRNAs in Cancer. Int J Mol Sci. 2018;19(2):459. DOI: 10.3390/ijms19020459Ramassone A., Pagotto S., Veronese A., Visone R. Epigenetics and MicroRNAs in Cancer // Int. J. Mol. Sci. 2018. Vol. 19, No. 2. P. 459. DOI: 10.3390/ijms19020459Jenuwein T. Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol. 2001;11(6):266–273. DOI: 10.1016/S0962-8924(01)02001-3Jenuwein T. Re-SET-ting heterochromatin by histone methyltransferases // Trends Cell. Biol. 2001. Vol. 11, No. 6. P. 266–273. DOI: 10.1016/S0962-8924(01)02001-3Kanwar JR, Roy K, Patel Y, et al. Multifunctional iron bound lactoferrin and nanomedicinal approaches to enhance its bioactive functions. Molecules. 2015;20(6):9703–9731. DOI: 10.3390/molecules20069703Kanwar J.R., Roy K., Patel Y. et al. Multifunctional iron bound lactoferrin and nanomedicinal approaches to enhance its bioactive functions // Molecules. 2015. Vol. 20, No. 6. P. 9703–9731. DOI: 10.3390/molecules20069703Sorensen M, Sorensen SPL. The Proteins in whey. Compt Rendus Trav Lab Carlsberg. 1940;23(7):55–99.Sorensen M., Sorensen S.P.L. The Proteins in whey // Compt. Rendus. Trav. Lab. Carlsberg. 1940. Vol. 23, No. 7. P. 55–99.Johansson B. Isolation of an iron-containing red protein from human milk. Acta Chem Scand. 1960;14:510–512. DOI: 10.3891/acta.chem.scand.14-0510Johansson B. Isolation of an iron-containing red protein from human milk // Acta Chem. Scand. 1960. Vol. 14. P. 510–512. DOI: 10.3891/acta.chem.scand.14-0510Yount NY, Andrés MT, Fierro JF, Yeaman MR. The γ-core motif correlates with antimicrobial activity in cysteine-containing kaliocin-1 originating from transferrins. Biochim Biophys Acta. 2007;1768(11):2862–2872. DOI: 10.1016/j.bbamem.2007.07.024Yount N.Y., Andrés M.T., Fierro J.F., Yeaman M.R. The γ-core motif correlates with antimicrobial activity in cysteine-containing kaliocin-1 originating from transferrins // Biochim. Biophys. Acta. 2007. Vol. 1768, No. 11. P. 2862–2872. DOI: 10.1016/j.bbamem.2007.07.024Ellison 3rd RT, Giehl TJ. Killing of gram-negative bacteria by lactoferrin and lysozyme. J Clin Invest. 1991;88(4):1080–1091. DOI: 10.1172/JCI115407Ellison 3rd R.T., Giehl T.J. Killing of gram-negative bacteria by lactoferrin and lysozyme // J. Clin. Invest. 1991. Vol. 88, No. 4. P. 1080–1091. DOI: 10.1172/JCI115407Hwang S, Chung IY, Jo J, et al. Comparison of proliferative effect of human lactoferrin and its proteolytic peptide on normal and transformed epithelial cells. Appl Biochem Biotechnol. 2016;178:44–57. DOI: 10.1007/s12010-015-1857-yHwang S., Chung I.Y., Jo J. et al. Comparison of proliferative effect of human lactoferrin and its proteolytic peptide on normal and transformed epithelial cells // Appl. Biochem. Biotechnol. 2016. Vol. 178. P. 44–57. DOI: 10.1007/s12010-015-1857-yGonzalez-Chavez SA, Arevalo-Gallegos S, Rascon-Cruz Q. Lactoferrin: structure, function and applications. Int J Antimicrob Agents. 2009;33(4):301.e1–301.e8. DOI: 10.1016/j.ijantimicag.2008.07.020Gonzalez-Chavez S.A., Arevalo-Gallegos S., Rascon-Cruz Q. Lactoferrin: structure, function and applications // Int. J. Antimicrob. Agents. 2009. Vol. 33, No. 4. P. 301.e1–301.e8. DOI: 10.1016/j.ijantimicag.2008.07.020Baker EN, Baker HM. Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci. 2005;62(22):2531–2539. DOI: 10.1007/s00018-005-5368-9Baker E.N., Baker H.M. Molecular structure, binding properties and dynamics of lactoferrin // Cell. Mol. Life Sci. 2005. Vol. 62, No. 22. P. 2531–2539. DOI: 10.1007/s00018-005-5368-9Furmanski P, Li Z, Fortuna MB, et al. Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity. J Exp Med. 1989;170(2):415–429. DOI: 10.1084/jem.170.2.415Furmanski P., Li Z., Fortuna M.B. et al. Multiple molecular forms of human lactoferrin. Identification of a class of lactoferrins that possess ribonuclease activity and lack iron-binding capacity // J. Exp. Med. 1989. Vol. 170, No. 2. P. 415–429. DOI: 10.1084/jem.170.2.415Baker EN. Structure and reactivity of transferrins. Adv Inorg Chem. 1994;41:389–463. DOI: 10.1016/S0898-8838(08)60176-2Baker E.N. Structure and reactivity of transferrins // Adv. Inorg. Chem. 1994. Vol. 41. P. 389–463. DOI: 10.1016/S0898-8838(08)60176-2Liu D, Wang X, Zhang Z, Teng CT. An intronic alternative promoter of the human lactoferrin gene is activated by Ets. Biochem Biophys Res Commun. 2003;301(2):472–479. DOI: 10.1016/S0006-291X(02)03077-2Liu D., Wang X., Zhang Z., Teng C.T. An intronic alternative promoter of the human lactoferrin gene is activated by Ets // Biochem. Biophys. Res. Commun. 2003. Vol. 301, No. 2. P. 472–479. DOI: 10.1016/S0006-291X(02)03077-2Mariller C, Hardivillé S, Hoedt E, et al. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor. Biochem Cell Biol. 2012;90(3):307–319. DOI:10.1139/o11-070Mariller C., Hardivillé S., Hoedt E. et al. Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor // Biochem. Cell. Biol. 2012. Vol. 90, No. 3. P. 307–319. DOI: 10.1139/o11-070Rubartelli A, Sitia R. Entry of exogenous polypeptides into the nucleus of living cells: facts and speculations. Trends Cell Biol. 1995;5(11):409–412. DOI: 10.1016/S0962-8924(00)89093-5Rubartelli A., Sitia R. Entry of exogenous polypeptides into the nucleus of living cells: facts and speculations // Trends Cell. Biol. 1995. Vol. 5, No. 11. P. 409–412. DOI: 10.1016/S0962-8924(00)89093-5Kanyshkova TG, Semenov DV, Buneva VN, Nevinsky GA. Human milk lactoferrin binds two DNA molecules with different affinities. FEBS Lett. 1999;451(3):235–237. DOI: 10.1016/S0014-5793(99)00579-7Kanyshkova T.G., Semenov D.V., Buneva V.N., Nevinsky G.A. Human milk lactoferrin binds two DNA molecules with different affinities // FEBS Lett. 1999. Vol. 451, No. 3. P. 235–237. DOI: 10.1016/S0014-5793(99)00579-7Verduci E, Banderali G, Barberi S, et al. Epigenetic effects of human breast milk. Nutrients. 2014;6(4):1711–1724. DOI: 10.3390/nu6041711Verduci E., Banderali G., Barberi S. et al. Epigenetic effects of human breast milk // Nutrients. 2014. Vol. 6, No. 4. P. 1711–1724. DOI: 10.3390/nu6041711Lebedev DV, Zabrodskaya YA, Pipich V, et al. Effect of alpha-lactalbumin and lactoferrin oleic acid complexes on chromatin structural organization. Biochem Biophys Res Commun. 2019;520(1):136–139. DOI: 10.1016/j.bbrc.2019.09.116Lebedev D.V., Zabrodskaya Y.A., Pipich V. et al. Effect of alpha-lactalbumin and lactoferrin oleic acid complexes on chromatin structural organization // Biochem. Biophys. Res. Commun. 2019. Vol. 520, No. 1. P. 136–139. DOI: 10.1016/j.bbrc.2019.09.116Zadvornyi TV, Lukianova NY, Borikun TV, Chekhun VF. Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human prostate cancer cells (DU145 and LNCaP) in vitro. Exp Oncol. 2018;40(3):184–189.Zadvornyi T.V., Lukianova N.Y., Borikun T.V., Chekhun V.F. Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human prostate cancer cells (DU145 and LNCaP) in vitro // Exp. Oncol. 2018. Vol. 40, No. 3. P. 184–189.Danforth DN, Sgagias MK. Interleukin-1α and interleukin-6 act additively to inhibit growth of MCF-7 breast cancer cells in vitro. Cancer Res. 1993;53(7):1538–1545.Danforth D.N., Sgagias M.K. Interleukin-1α and interleukin-6 act additively to inhibit growth of MCF-7 breast cancer cells in vitro // Cancer Res. 1993. Vol. 53, No. 7. P. 1538–1545.Mishra S, Tai Q, Gu X, et al. Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer. Oncotarget. 2015;6(42):44388–44402. DOI: 10.18632/oncotarget.6317Mishra S., Tai Q., Gu X. et al. Estrogen and estrogen receptor alpha promotes malignancy and osteoblastic tumorigenesis in prostate cancer // Oncotarget. 2015. Vol. 6, No. 42. P. 44388–44402. DOI: 10.18632/oncotarget.6317Fleisch AF, Wright RO, Baccarelli AA. Environmental epigenetics: a role in endocrine disease? J Mol Endocrinol. 2012;49(2):R61–R67. DOI: 10.1530/JME-12-0066Fleisch A.F., Wright R.O., Baccarelli A.A. Environmental epigenetics: a role in endocrine disease? // J. Mol. Endocrinol. 2012. Vol. 49, No. 2. P. R61–R67. DOI: 10.1530/JME-12-0066Kovács T, Szabó-Meleg E, Ábrahám I. Estradiol-induced epigenetically mediated mechanisms and regulation of gene expression. Int J Mol Sci. 2020;21(9):3177. DOI: 10.3390/ijms21093177Kovács T., Szabó-Meleg E., Ábrahám I. Estradiol-induced epigenetically mediated mechanisms and regulation of gene expression // Int. J. Mol. Sci. 2020. Vol. 21, No. 9. P. 3177. DOI: 10.3390/ijms21093177Ariazi E, Taylor J, Black M, et al. A new role for ERα: Silencing via DNA methylation of basal, stem cell, and EMT genes. Mol Cancer Res. 2017;15(2):152–164. DOI: 10.1158/1541-7786.mcr-16-0283Ariazi E., Taylor J., Black M. et al. A new role for ERα: Silencing via DNA methylation of basal, stem cell, and EMT genes // Mol. Cancer Res. 2017. Vol. 15, No. 2. P. 152–164. DOI: 10.1158/1541-7786.mcr-16-0283Jin X, Li Y, Guo Y, et al. ERα is required for suppressing OCT4-induced proliferation of breast cancer cells via DNMT1/ISL1/ERK axis. Cell Prolif. 2019;52(4):e12612. DOI: 10.1111/cpr.12612Jin X., Li Y., Guo Y. et al. ERα is required for suppressing OCT4-induced proliferation of breast cancer cells via DNMT1/ISL1/ERK axis // Cell. Prolif. 2019. Vol. 52, No. 4. P. e12612. DOI: 10.1111/cpr.12612Wang L, Ozark P, Smith E, et al. TET2 coactivates gene expression through demethylation of enhancers. Sci Adv. 2018;4(11):eaau6986. DOI: 10.1126/sciadv.aau6986Wang L., Ozark P., Smith E. et al. TET2 coactivates gene expression through demethylation of enhancers // Sci. Adv. 2018. Vol. 4, No. 11. P. eaau6986. DOI: 10.1126/sciadv.aau6986Reale E, Taverna D, Cantini L, et al. Investigating the epi-miRNome: identification of epi-miRNAs using transfection experiments. Epigenomics. 2019;11(14):1581–1599. DOI: 10.2217/epi-2019-0050Reale E., Taverna D., Cantini L. et al. Investigating the epi-miRNome: identification of epi-miRNAs using transfection experiments // Epigenomics. 2019. Vol. 11, No. 14. P. 1581–1599. DOI: 10.2217/epi-2019-0050Di Croce L, Helin K. Transcriptional regulation by Polycomb group proteins. Nat Struct Mol Biol. 2013;20(10):1147–1155. DOI: 10.1038/nsmb.2669Di Croce L., Helin K. Transcriptional regulation by Polycomb group proteins // Nat. Struct. Mol. Biol. 2013. Vol. 20, No. 10. P. 1147–1155. DOI: 10.1038/nsmb.2669Nuytten M, Beke L, Van Eynde A, et al. The transcriptional repressor NIPP1 is an essential player in EZH2-mediated gene silencing. Oncogene. 2008;27(10):1449–1460. DOI: 10.1038/sj.onc.1210774Nuytten M., Beke L., Van Eynde A. et al. The transcriptional repressor NIPP1 is an essential player in EZH2-mediated gene silencing // Oncogene. 2008. Vol. 27, No. 10. P. 1449–1460. DOI: 10.1038/sj.onc.1210774Williams LV, Veliceasa D, Vinokour E, Volpert OV. miR-200b inhibits prostate cancer EMT, growth and metastasis. PLoS One. 2013;8(12):e83991. DOI: 10.1371/journal.pone.0083991Williams L.V., Veliceasa D., Vinokour E., Volpert O.V. miR-200b inhibits prostate cancer EMT, growth and metastasis // PLoS One. 2013. Vol. 8, No. 12. P. e83991. DOI: 10.1371/journal.pone.0083991Kojima S, Chiyomaru T, Kawakami K, et al. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer. Br J Cancer. 2012;106(2):405–413. DOI: 10.1038/bjc.2011.462Kojima S., Chiyomaru T., Kawakami K. et al. Tumour suppressors miR-1 and miR-133a target the oncogenic function of purine nucleoside phosphorylase (PNP) in prostate cancer // Br. J. Cancer. 2012. Vol. 106, No. 2. P. 405–413. DOI: 10.1038/bjc.2011.462Chavali V, Tyagi SC, Mishra PK. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. Biochem Biophys Res Commun. 2012;425(3):668–672. DOI: 10.1016/j.bbrc.2012.07.105Chavali V., Tyagi S.C., Mishra P.K. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes // Biochem. Biophys. Res. Commun. 2012. Vol. 425, No. 3. P. 668–672. DOI: 10.1016/j.bbrc.2012.07.105Liu J, Zhang X, Huang Y, et al. miR-200b and miR-200c co-contribute to the cisplatin sensitivity of ovarian cancer cells by targeting DNA methyltransferases. Oncol Lett. 2019;17(2):1453–1460. DOI: 10.3892/ol.2018.9745Liu J., Zhang X., Huang Y. et al. miR-200b and miR-200c co-contribute to the cisplatin sensitivity of ovarian cancer cells by targeting DNA methyltransferases // Oncol. Lett. 2019. Vol. 17, No. 2. P. 1453–1460. DOI: 10.3892/ol.2018.9745Guo C, Yang Z-H, Zhang S, et al. Intranasal lactoferrin enhances α-secretase-dependent amyloid precursor protein processing via the ERK1/2-CREB and HIF-1α pathways in an Alzheimer’s disease mouse model. Neuropsychopharmacology. 2017;42(13):2504–2515. DOI: 10.1038/npp.2017.8Guo C., Yang Z.-H., Zhang S. et al. Intranasal lactoferrin enhances α-secretase-dependent amyloid precursor protein processing via the ERK1/2-CREB and HIF-1α pathways in an Alzheimer’s disease mouse model // Neuropsychopharmacology. 2017. Vol. 42, No. 13. P. 2504–2515. DOI: 10.1038/npp.2017.8Malm T, Koistinaho J, Kanninen K. Utilization of APPswe/PS1dE9 transgenic mice in research of Alzheimer’s disease: Focus on gene therapy and cell-based therapy applications. Int J Alzheimers Dis. 2011:517160. DOI: 10.4061/2011/517160Malm T., Koistinaho J., Kanninen K. Utilization of APPswe/PS1dE9 transgenic mice in research of Alzheimer’s disease: Focus on gene therapy and cell-based therapy applications // Int. J. Alzheimers Dis. 2011. P. 517160. DOI: 10.4061/2011/517160Taher N, McKenzie C, Garrett R, et al. Amyloid-β alters the DNA methylation status of cell-fate genes in an Alzheimer’s disease model. J Alzheimers Dis. 2014;38(4):831–844. DOI: 10.3233/JAD-131061Taher N., McKenzie C., Garrett R. et al. Amyloid-β alters the DNA methylation status of cell-fate genes in an Alzheimer’s disease model // J. Alzheimers Dis. 2014. Vol. 38, No. 4. P. 831–844. DOI: 10.3233/JAD-131061Grau AJ, Willig V, Fogel W, Werle E. Assessment of plasma lactoferrin in Parkinson’s disease. Mov Disord. 2001;16(1):131–134. DOI: 10.1002/1531-8257(200101)16:1<131::aid-mds1008>3.0.co;2-oGrau A.J., Willig V., Fogel W., Werle E. Assessment of plasma lactoferrin in Parkinson’s disease // Mov. Disord. 2001. Vol. 16, No. 1. P. 131–134. DOI: 10.1002/1531-8257(200101)16:1<131::aid-mds1008>3.0.co;2-oSokolov AV, Miliukhina IV, Belsky YuP, et al. Potential role of lactoferrin in early diagnostics and treatment of Parkinson disease. Medical Academic Journal. 2020;20(1):37–44. DOI: 10.17816/MAJ33848Sokolov A.V., Miliukhina I.V., Belsky Yu.P. et al. Potential role of lactoferrin in early diagnostics and treatment of Parkinson disease // Medical Academic Journal. 2020. Vol. 20, No. 1. P. 37–44. DOI: 10.17816/MAJ33848Zalutski IV, Lukianova NY, Storchai DM, et al. Influence of exogenous lactoferrin on the oxidant/ antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro. Exp Oncol. 2017;39(2):106–111.Zalutski I.V., Lukianova N.Y., Storchai D.M. et al. Influence of exogenous lactoferrin on the oxidant/ antioxidant balance and molecular profile of hormone receptor-positive and -negative human breast cancer cells in vitro // Exp. Oncol. 2017. Vol. 39, No. 2. P. 106–111.Zakharova E, Kostevich V, Sokolov A, Vasilyev V. Human apo-lactoferrin as a physiological mimetic of hypoxia stabilizes hypoxia-inducible factor-1 alpha. Biometals. 2012;25(6):1247–1259. DOI: 10.1007/s10534-012-9586-yZakharova E., Kostevich V., Sokolov A., Vasilyev V. Human apo-lactoferrin as a physiological mimetic of hypoxia stabilizes hypoxia-inducible factor-1 alpha // Biometals. 2012. Vol. 25, No. 6. P. 1247–1259. DOI: 10.1007/s10534-012-9586-yLuo W, Chang R, Zhong J, et al. Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression. Proc Natl Acad Sci USA. 2012;109(49):E3367–E3376. DOI: 10.1073/pnas.1217394109Luo W., Chang R., Zhong J. et al. Histone demethylase JMJD2C is a coactivator for hypoxia-inducible factor 1 that is required for breast cancer progression // Proc. Natl. Acad. Sci. USA. 2012. Vol. 109, No. 49. P. E3367–E3376. DOI: 10.1073/pnas.1217394109Skowronski K, Dubey S, Rodenhiser D, Coomber B. Ischemia dysregulates DNA methyltransferases and p16INK4a methylation in human colorectal cancer cells. Epigenetics. 2010;5(6):547–556. DOI: 10.4161/epi.5.6.12400Skowronski K., Dubey S., Rodenhiser D., Coomber B. Ischemia dysregulates DNA methyltransferases and p16INK4a methylation in human colorectal cancer cells // Epigenetics. 2010. Vol. 5, No. 6. P. 547–556. DOI: 10.4161/epi.5.6.12400Patterson A, Chen M, Xue Q, et al. Chronic prenatal hypoxia induces epigenetic programming of PKCε gene repression in rat hearts. Circ Res. 2010;107(3):365–373. DOI: 10.1161/circresaha.110.221259Patterson A., Chen M., Xue Q. et al. Chronic prenatal hypoxia induces epigenetic programming of PKCε gene repression in rat hearts // Circ. Res. 2010. Vol. 107, No. 3. P. 365–373. DOI: 10.1161/circresaha.110.221259Thienpont B, Steinbacher J, Zhao H, et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity. Nature. 2016;537(7618):63–68. DOI: 10.1038/nature19081Thienpont B., Steinbacher J., Zhao H. et al. Tumour hypoxia causes DNA hypermethylation by reducing TET activity // Nature. 2016. Vol. 537, No. 7618. P. 63–68. DOI: 10.1038/nature19081Akanji M, Rotimi D, Adeyemi O. Hypoxia-inducible factors as an alternative source of treatment strategy for cancer. Oxid Med Cell Longev. 2019:8547846. DOI: 10.1155/2019/8547846Akanji M., Rotimi D., Adeyemi O. Hypoxia-inducible factors as an alternative source of treatment strategy for cancer // Oxid. Med. Cell. Longev. 2019. P. 8547846. DOI: 10.1155/2019/8547846Wang G, Jiang B, Rue E, Semenza G. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 1995;92(12):5510–5514. DOI: 10.1073/pnas.92.12.5510Wang G., Jiang B., Rue E., Semenza G. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension // Proc. Natl. Acad. Sci. USA. 1995. Vol. 92, No. 12. P. 5510–5514. DOI: 10.1073/pnas.92.12.5510Kostevich V, Sokolov A, Zakharova E, Vasilyev V. Apolactoferrin in mother’s milk induces HIF signaling in neonate animals. Am J Perinatol. 2018;35(S 01):S1–S26. DOI: 10.1055/s-0038-1647102Kostevich V., Sokolov A., Zakharova E., Vasilyev V. Apolactoferrin in mother’s milk induces HIF signaling in neonate animals // Am. J. Perinatol. 2018. Vol. 35, No. S 01. P. S1–S26. DOI: 10.1055/s-0038-1647102Bellamy W, Takase M, Wakabayashi H, et al. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin. J Appl Bacteriol. 1992;73(6):472–479. DOI: 10.1111/j.1365-2672.1992.tb05007.xBellamy W., Takase M., Wakabayashi H. et al. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin // J. Appl. Bacteriol. 1992. Vol. 73, No. 6. P. 472–479. DOI: 10.1111/j.1365-2672.1992.tb05007.xLizzi A, Carnicelli V, Clarkson M, et al. Lactoferrin derived peptides: mechanisms of action and their perspectives as antimicrobial and antitumoral agents. Mini Rev Med Chem. 2009;9(6):687–695. DOI: 10.2174/138955709788452757Lizzi A., Carnicelli V., Clarkson M. et al. Lactoferrin derived peptides: mechanisms of action and their perspectives as antimicrobial and antitumoral agents // Mini Rev. Med. Chem. 2009. Vol. 9, No. 6. P. 687–695. DOI: 10.2174/138955709788452757Zhang T-N, Liu N. Effect of bovine lactoferricin on DNA methyltransferase 1 levels in Jurkat T-leukemia cells. J Dairy Sci. 2010;93(9):3925–3930. DOI: 10.3168/jds.2009-3024Zhang T.-N., Liu N. Effect of bovine lactoferricin on DNA methyltransferase 1 levels in Jurkat T-leukemia cells // J. Dairy Sci. 2010. Vol. 93, No. 9. P. 3925–3930. DOI: 10.3168/jds.2009-3024