Gebelik Sürecinde Rol Oynayan mikroRNA (miRNA)’lar

Yıl 2019, Cilt: 59 Sayı: 1, 36 - 48, 02.07.2019

Özge Sidekli , Özgecan Korkmaz Ağaoğlu

Öz

MikroRNA (miRNA)’lar, çok hücreli organizmalarda mesajcı RNA (mRNA)’nın translasyonunu etkileyerek, gen ekspresyonunu postranskripsiyonel aşamada düzenleyen kısa, 17-25 nükleotid uzunluğunda, kodlama yapmayan küçük RNA molekülleridir. miRNA’lar, kendi nü kleotid dizilerinin tamamlayıcısı olan hedef mRNA’lara bağ lanıp gen ekspresyonunu baskılamakta veya tamamen ortadan kaldırmaktadır. Böylece; gen ekspresyonunun düzenlenmesini gerçekleştirmektedirler. miRNA’lar; hü crelerin proliferasyonu, farklılaşması ve ö lü mü gibi süreçlerde oldukça önemli roller üstlenmektedirler. Son yıllarda yapılan çalışmalar ile birlikte miRNA’ların; gebeliğin oluşumu ve sürdürülebilmesi de dâhil olmak üzere anjiyogenezis, yangısal yanıt ve hipoksi gibi hücresel ve moleküler aktivite ile ilişkili genlerin kontrolünde önemli düzenleyici rollere sahip oldukları bildirilmiştir. Gebelik ile ilişkili miRNA’ların büyük bir kısmının reprodüktif dokularda eksprese olduğu ortaya konmuştur. Gebelik süreci içinde miRNA biyogenezinin epigenetik etkilerinin molekü ler dü zeyde ortaya konması, gebeliğin mekanizmasının aydınlatılması açısından önemli bir potansiyel taşımaktadır. Bu derlemede; gebelik sürecinde aktif rol alan miRNA’lar ve miRNA’ların bu fizyolojik sürece katkıları hakkında bilgiler özetlenmiştir.

Anahtar Kelimeler

mikroRNA, gebelik, uterus

Kaynakça

• 1. Agaoglu OK, Agaoglu AR, Guzeloglu A, Kurar E, Kayis SA, Ozmen O, Schäfer-Somi S, Aslan S (2015): Expression of hypoxia-inducible factors and vascular endothelial growth factor during pregnancy in the feline uterus. Theriogenology, 84: 24-33.
• 2. Altmäe S, Martinez-Conejero JA, Esteban FJ, Ruiz-Alonso M, Stavreus- Evers A, Horcajadas JA, Salumets A (2013): MicroRNAs miR-30b, miR-30d, and miR-494 regulate human endometrial receptivity. Reprod Sci., 20: 308–317.
• 3. Bae IS, Chung KY, Yi J, Kim T, Choi HS, Cho YM, Choi I, Kim SH (2015): Identification of reference genes for relative quantification of circulating microRNAs in bovine serum. Plos One, 31;10(3):e0122554.
• 4. Bidarimath M, Khalaj K, Wessels JM, Tayade C (2014): MicroRNAs, immune cells and pregnancy. Cell Mol İmmunology.,11, 538–547.
• 5. Cai M, Kolluru GK, Ahmed A (2017): Small Molecule, Big Prospects: MicroRNA in Pregnancy and Its Complications. J pregnancy., (17):69.
• 6. Carletti MZ, Christenson LK (2009): MicroRNA in the ovary and female reproductive tract. J Anim Sci., 87(14): 29-38.
• 7. Chakrabarty A, Tranguch S, Daikoku T, Jensen K, Furneaux H, Dey SK (2007): MicroRNA regulation of cyclooxygenase-2 during embryo implantation. Proc Natl Acad Sci., (104)38:15144-15149.
• 8. Chan HW, Lappas M, Yee SWY, Vaswani K, Mitchell MD ve Rice GE (2013): The expression of the let-7 miRNAs and Lin28 signalling pathway in human term gestational tissues. Placenta, 34(5): 443–448.
• 9. Chegini N (2010): Uterine microRNA signature and consequence of their dysregulation in uterine disorders. Anim Reprod., 7(3):117- 128.
• 10. Chim SSC, Shing TKF, Hungetal ECW (2008): Detectionand characterization of placental microRNAs in maternal plasma, Clin Chem., 54(3): 482–490.
• 11. Cuman C, Van Sinderen M, Gantier MP, Rainczuk K, Sorby K, Rombauts L (2015): Human blastocyst secreted microRNA regulate endometrial epithelial cell adhesion. EBioMedicine., 2(10):1528–35.
• 12. Dammer EB, Sewer MB (2008): Phosphorylation of CTBP1 by cAMP-dependent protein kinase modulates induction of cyp17 by stimulating partnering of CTBP1 and 2. J Biol Chem., 283:6925– 6934.
• 13. Ding J, Huang F, Wu G (2015): MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP- 2. PLoS ONE, 10(3): e0120321
• 14. Dini P, Loux SC, Scoggin KE, Esteller-Vico A, Squires E, Troedsson MHT, Daels P, Ball BA (2018): Identification of Reference Genes for Analysis of microRNA Expression Patterns in Equine Chorioallantoic. Mol Biotechnol., 60(1): 62-73
• 15. Doebele C, Bonauer A, Fischer A, Scholz A, Reiss Yve Urbich C (2010): Members of the microRNA-17-92 cluster exhibit a cellintrinsic antiangiogenic function in endothelial cells. Blood., 115: 4944–4950.
• 16. Doridot L, Miralles F, Barbaux S, Vaiman D (2013): Trophoblasts, invasion, and microRNA. Front Genet., 4:248.
• 17. Fiedler SD, Carletti MZ Hong X, Christenson LK (2008): Hormonal regulation of MicroRNA expression in periovulatory mouse mural granulosa cells. Biol. Reprod., 79: 1030–1037.
• 18. Flor I, Bullerdiek J (2012): The dark side of a success story: microR- NAs of the C19MC cluster in human tumours. J. Pathol., 227: 270–274.
• 19. Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, Liuzzi F, Croce CM, Brunetti E, Grignani F, Peschle C (2007): MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M- CSF receptor upregulation. Nat Cell Biol., 9:775–787.
• 20. Fu G, Brkic J, Hayder H ve Peng C (2013): MicroRNAs in Human Placental Development and Pregnancy Complications. Int J Mol Sci., 14(3):5519-44.
• 21. Fu TY, Lin CT, Tang PC (2011): Steroid hormone regulated let-7b mediates cell proliferation and basigin expression in the mouse endometrium. J Reprod Dev., 57(5): 627–635.
• 22. Goyal R, Lister R, Leitzke A, Goyal D, Gheorghe CP, Longo LD (2010): Brain rennin-angiotensin system: fetal epigenetic programming by maternal protein restriction. Reprod sci., 17(3):227-38.
• 23. Gross N, Kropp J, Khatib H (2017): MicroRNA Signaling in Embryo Development. Biology., 14:6(3).
• 24. Guo H, Ingolia NT, Weissman JS, Bartel DP (2010): Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature., 466(7308): 835–840.
• 25. Hawkins SM, Andreu-Vieyra CV, Kim TH (2012): Dysregulation of uterine signaling pathways in progesterone receptor- cre knockout of dicer, Mol Endocrinol., 26(9): 1552–1566.
• 26. Hosseini MK, Gunel T, Gumusoglu E, Benian A, Aydınlı K (2018): MicroRNA expression profiling in placenta and maternal plasma in early pregnancy loss. Mol Med Rep.,17:4941-4952.
• 27. Hu SJ, Ren G, Liuetal JL (2008): MicroRNA expression and regulation in mouse uterus during embryo implantation. J Biol Chem., 283(34):23473–23484.
• 28. Inyawilert W, Lin CT, Tang PC (2014): MicroRNA-199a mediates mucin 1 expression in mouse uterus during implantation. Reprod Fertil Dev., 26(5):653–64.
• 29. Ioannidis J, Donadeu FX (2016): Circulating miRNA signatures of early pregnancy in cattle. BMC Genomics., 17:184.
• 30. Kelly TJ, Souza AL, Clish CB, Puigserver PA (2011): Hypoxiainduced positive feedback loop promotes hypoxia-inducible factor 1alpha stability through miR-210 suppression of glycerol-3-phosphate dehydrogenase 1-like. Mol Cell Biol, 31(3): 2696–2706.
• 31. Keniry A, Oxley D, Monnier P (2012): The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat Cell Biol., 14(7): 659–665
• 32. Khorram O, Chuang TD ve Pearce WJ (2015): Long-term effects of maternal undernutrition on offspring carotid artery remodelling:role of miR-29c. J Dev Orig Health Dis., 6(4):342-9.
• 33. Klohonatz KM, Cameron AD, Hergenreder JR, Silveira JC, Belk AD, Veeramevhaneni DNR, Bouma GJ, Bruemmer JE (2016): Circulating miRNAs as Potential Alternative Cell Signaling Associated with Maternal Recognition of Pregnancy in the Mare. Bio Repr., 95(6):124, 1-12.
• 34. Kotlabova K (2011): Placental-specific microRNA in maternal circulation identification of appropriate pregnancy-associated microRNAs with diagnostic potential. J Reprod Immunol., 89(2): 185–191.
• 35. Kozomara A, Birgaoanu M, Jones-Griffiths S (2019): miRBase: from microRNA sequences to function. Nucleic Asids Res., 47: 155-162.
• 36. Li P, Guo W, Zhao J (2013): MicroRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells. Clin Sci., 124(1):27-40.
• 37. Li X, Li C, Dong X ve Gou W (2014): MicroRNA-155 inhibits migration of trophoblast cells and contributes to the pathogenesis of severe preeclampsia by regulating endothelial nitric oxide synthase, Mol Med Rep., 10(1): 550– 554
• 38. Liang J, Wang S ve Wang Z (2017): Role of microRNAs in embriyo implantation. Reprod Biol Endocrinol., 15:90.
• 39. Liu L, Wang Y, Fan H (2012): MicroRNA-181a regulates local immune balance by inhibiting proliferation and immunosuppressive properties of mesenchymal stem cells, Stem Cells., 30(8):1756– 1770.
• 40. Liu WM, Pang RT, Cheong AW, Ng EH, Lao K, Lee KF (2012b): Involvement of microRNA lethal-7a in the regulation of embryo implantation in mice. PLoS One.,7(5):37039.
• 41. Liu X, Zhan Z, Xu L (2010): MicroRNA-148/152 impair innate response and antigen presentation of TLR-triggered dendritic cells by targeting CaMKIIα. J Immunol., 185(12): 7244–7251
• 42. Lu T, Lu W, Zhao L (2017): MicroRNA-137 affects proliferation and migration of placenta trophoblast cells in preeclampsia by targeting ERRα. Reprod Sci., 24(1): 85–96.
• 43. Luo L, Ye G, Nadeem L (2012): Microrna-378a-5p promotes trophoblast cell survival, migration and invasion by targeting Nodal. J Cell Sci., 125(13): 3124–3132.
• 44. Melo CA, Melo SA (2014): Biogenesis and Physiology of MicroRNAs. Springer., 5-24.
• 45. Miura K, Morisaki S, Abe S, Higashijima A, Hasegawa Y, Miura S, Tateishi S, Mishima H, Yoshiura K ve Masuzaki H (2014): Circulating levels of maternal plasma cell-free pregnancy-associated placenta-specific microRNAs are associated with placental weight. Placenta, 35:848-851.
• 46. Morales-Prieto DM, Ospina-Prieto S, Chaiwangyen W, Schoenleben M ve Markert UR (2013): Pregnancy-associated miRNA-clusters. J Reprod Immunol., 97(1): 51–6.1
• 47. Morales-Prieto DM, Schleussner E, Markert UR (2011): Reduction in miR-141 is induced by leukemia inhibitory factor and inhibits proliferation in choriocarcinoma cell line JEG-3. Am J Reprod Immunol., 66(1): 57–62.
• 48. Morales-Prieto, DM, Chaiwangyen W, Ospina-Prieto S, Schneider U, Herrmann J, Gruhn B, Markert UR (2012): MicroRNA expression profiles of trophoblastic cells. Placenta., 33: 725–734.
• 49. Mouillet JF, Chu T, Hubel CA, Nelson DM, Anthony P, Sadovsky Y (2010): The levels of hypoxia-regulated microRNAs in plasma of pregnanct women with fetal growth restriction. Placenta., 31(9):781-784.
• 50. Mouillet JF, Donker RB, Mishima T, Cronqvist T, Chu T ve Sadovsky Y (2013): The unique expression and function of miR- 424 in human placental trophoblasts, Biol Reprod., 89(2): 25.
• 51. Nothnick WB, Healy C (2010): Estrogen induces distinct patterns of microRNA expression within the mouse uterus. Reprod Sci., 17: 987–994.
• 52. Nothnick WB, Healy C, Hong X (2010b): Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1. Endocr., 37:265–273.
• 53. Ouyang Y, Mouillet JF, Coyne CB, Sadovsky Y (2014): Plasentaspecific microRNAs in exosomes-good things come in nano packages. Placenta., 35:69-73.
• 54. Pernaute B, Spruce T, Rodriguez TA, Manzanares M (2011): MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo. Cell Cycle, 10(4):584–91.
• 55. Qian K, Hu L, Chen H, Li H, Liu N, Li Y, Zhu G, Tang Z, Zhang H (2009): Hsa-miR-222 is involved in differentiation of endometrial stroma cells in vitro. Endocrinology., 150(10):4734-43.
• 56. Reliszko ZP, Gajewski Z, Kaczmarek MM (2017): Signs of embryo- maternal communication: miRNAs in the maternal serum of pregnant pigs. Reproduction, 154: 117-128.
• 57. Schlabritz N, Apostolakıs K ve Dıck E (2016): Pregnancy-Driven cardiovascular maternal miR-29 plasticity in obesity., J Med Primatol., 45(6):297-303.
• 58. Serocki M, Bartoszewska S, Jasiecka Janaszak A, Ochcka RJ, Collawn JF, Bartoszewski R (2017): miRNAs regulate the HIF switch during hypoxia: a novel therapeutic target. Angiogenesis., 21:183-202.
• 59. Sinha PB, Tesfaye D, Rings F, Hossien M, Hoelker M, Held E (2017): MicroRNA- 130b is involved in bovine granulosa and cumulus cells function, oocyte maturation and blastocyst formation. J Ovarian Res., 10(1):37.
• 60. Song Y, An X, Zhang L, Fu M, Peng J, Han P, Hou J, Zhou Z, Cao B (2015): Identification and Profiling of microRNAs in Goat Endometrium during Embryo Implantation. Plos One, 0(4): 0122202.
• 61. Su L, Zhao S, Zhu M ve Yu M (2010): Differential expression of microRNAs in porcine placentas on Days 30 and 90 of gestation. Reprod Fertil Dev., 22(8): 1175–1182.
• 62. Suarez Y, Fernandez-Hernando C, Pober JS, Sessa WC (2007): Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res., 100:1164–1173.
• 63. Taganov KD, Boldin MP, Baltimore D (2007): MicroRNAs and immunity: tiny players in a big field. Immunity., 26:133–137.
• 64. Tang F, Kaneda M, O’Carroll D, Hajkova P, Barton SC, Sun YA, Lee C, Tarakhovsky A, Lao K, Surani MA (2007): Maternal microRNAs are essential for mause zygotic development. Genes Dev., 21:644-648.
• 65. Tesfaye D, Worku D, Rings F, Phatsara C, Tholen E, Schellander K (2009): Identification and expression profiling of microRNAs during bovine oocyte maturation using heterologous approach. Mol Reprod Dev., 76(7): 665–77.
• 66. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, Fabbri M, Alder H, Liu CG, Calin GA, Croce CM (2007): Modulation of miR-155 and miR-125b levels following lipopolysaccharide/ TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol., 179:5082–5089.
• 6. Vural R, Güzeloğlu A, Küplülü Ş (2012): Gebelik Fizyolojisi. s:125- 156. Çiftlik Hayvanlarında Doğum ve Jinekoloji, Edit: Semacan A, Kaymaz M, Fındık M, Rişvanlı A, Köker. A., Medipress Yayıncılık Ltd Şti., Malatya.
• 68. Wang W, Feng L, Zhang H, Hachy S, Satohisa S, Laurent LC (2012): Preeclampsia up-regulates angiogenesis-associated microRNA (i.e., miR- 17, -20a, and -20b) that target ephrin-B2 and EPHB4 in human placenta. J. Clin. Endocrinol. Metab., 97:E1051–E1059.
• 69. Wang Y, Fan H, Zhao G, Liu D, Du L, Wang Z, Hu Y, Hou Y (2012b): MiR-16 inhibits the proliferation and angiogenesis-regulating potential of mesenchymal stem cells in severe pre-eclampsia. FEBS J., 289, 4510–4524.
• 70. Wessels JM, Edwards AK, Khalaj K, Kridli RT, Bidarimath M ve Tayade C (2013): The MicroRNAome of Pregnancy: Deciphering miRNA Networks at the Maternal-Fetal Interface, Plos One., 8(11):72264.
• 71. Williams Z, Ben-Dov IZ, Elias R (2013): Comprehensive profiling of circulating microRNA via small RNA sequencing of cDNA libraries reveals biomarker potential and limitations. Proc Natl Acad Sci USA., 110(11):4255–4260.
• 72. Xia HF, Jin XH, Cao ZF, Hu Y, Ma X (2014): MicroRNA expression and regulation in the uterus during embryo implantation in rat. FEBS J., 281: 1872–1891.
• 73. Yang Y, Xie Y, Wu M, Geng Y, Li R ve Xu L (2017):Expression of mmu-miR-96 in the endometrium during early pregnancy and its regulatory effects on stromal cell apoptosis via Bcl2. Mol Med Rep., 15(4):1547–54.
• 74. Yuan S, Schuster A, Tang C, Yu T, Ortogero N, Bao J, Zheng H, Yan W (2016): Sperm-borne miRNAs and endo-siRNAs are important for fertilization and preimplantation embryonic development. Development., 143: 635–647.
• 75. Zhang Q, Zhang H, Jiang Y, Xue B, Diao Z ve Ding L (2015): MicroRNA-181a is involved in the regulation of human endometrial stromal cell decidualization by inhibiting Kruppel-like factor 12. Reprod Biol Endocrinol., 13:23.
• 76. Zhang S, Lin H, Kong S, Wang S, Wang H (2013): Physiological and molecular determinants of embryo implantation. Mol Asp Med., 34(5):939-80.
• 77. Zheng CY, Zou X, Lin HJ, Zhou BC, Zhang ML, Luo CH, Fu SX (2018): miRNA-185 regulates the VEGFA signaling pathway in dairy cows with retained fetal membranes. Theriogenology., 110:116-121.
• 78. Zou Y, Jiang Z, Yu X (2014): MiR-101 regulates apoptosis of trophoblast HTR-8/SVneo cells by targeting endoplasmic reticulum (ER) protein 44 during preeclampsia. J Hum Hypertens., 28(10):610–616.