Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

MicroRNAs Associated with Preeclampsia

  • 8 Accesses


MicroRNAs (miRNAs) are a class of small noncoding RNAs that play an important role in the mRNA regulation translation and degradation. Recent studies uncovered the implication of miRNA in the development of preeclampsia (PE)—a common and potentially fatal complication in pregnancy. This review provides an analysis of the current knowledge on miRNA associated with PE. We discuss the potential for using miRNA for the early diagnosis and prevention of PE. We briefly describe the miRNA targets associated with PE and point out the most promising PE predictors.

This is a preview of subscription content, log in to check access.

Fig. 1.


  1. 1

    Ailamazyan, E.K., Akusherstvo: natsional’noe rukovodstvo (Obstetrics: National Guidelines), Moscow: GEOTAR‑Media, 2009.

  2. 2

    Ailamazyan, E.K. and Mozgovaya, E.V., Gestoz: teoriya i praktika (Gestosis: Theory and Practice), Moscow: MEDpressinform, 2008.

  3. 3

    Vashukova, E.S., Molecular genetic aspects of preeclampsia among women in the North-West region of Russia, Cand. Sci. (Biol.) Dissertation, St. Petersburg: St. Petersburg State University, 2017.

  4. 4

    Guo, L., Yang, Q., Lu, J., et al., A comprehensive survey of miRNA repertoire and 3′ addition events in the placentas of patients with pre-eclampsia from high-throughput sequencing, PLoS One, 2011, vol. 6, no. 6, article ID e21072. https://doi.org/10.1371/journal.pone.0021072

  5. 5

    Murphy, M.S., Tayade, C., and Smith, G.N., Maternal circulating microRNAs and pre-eclampsia: challenges for diagnostic potential, Mol. Diagn. Ther., 2017, vol. 21, no. 1, pp. 23—30. https://doi.org/10.1007/s40291-016-0233-0

  6. 6

    Vlasova, S.P., Il’chenko, M.Yu., Kazakova, E.B., et al., Disfunktsiya endoteliya i arterial’naya gipertenziya (Endothelial Dysfunction and the Arterial Hypertension), Samara: Ofort, 2010.

  7. 7

    Chen, D.B. and Wang, W., Human placental microRNAs and preeclampsia, Biol. Reprod., 2013, vol. 88, no. 5, article ID 130. https://doi.org/10.1095/biolreprod.113.107805

  8. 8

    Lycoudi, A., Mavreli, D., Mavrou, A., et al., MiRNAs in pregnancy-related complications, Expert Rev. Mol. Diagn., 2015, vol. 15, no. 8, pp. 999—1010. https://doi.org/10.1586/14737159.2015.1053468

  9. 9

    Poirier, C., Desgagné, V., Guérin, R., and Bouchard, L., MicroRNAs in pregnancy and gestational diabetes mellitus: emerging role in maternal metabolic regulation, Curr. Diab. Rep., 2017, vol. 17, no. 5, p. 35. https://doi.org/10.1007/s11892-017-0856-5

  10. 10

    Li, T., Leong, M.H., Harms, B., et al., MicroRNA-21 as a potential colon and rectal cancer biomarker, World J. Gastroenterol., 2013, vol. 19, no. 34, pp. 5615—5621. https://doi.org/10.3748/wjg.v19.i34.5615

  11. 11

    Lv, Y., Lu, C., Ji, X., et al., Roles of microRNAs in preeclampsia, J. Cell Physiol., 2019, vol. 234, no. 2, pp. 1052—1061. https://doi.org/10.1002/jcp.27291

  12. 12

    Tiguntsev, V.V., Ivanova, S.A., Serebrov, V.Yu., and Bukhareva, M.B., Small non-coding RNAs as promising biomarkers: biogenesis and therapeutic strategies, Byull. Sib. Med., 2016, vol. 15, no. 2, pp. 112—126.

  13. 13

    Baulina, N.M., Kulakova, O.G., and Favorova, O.O., MicroRNAs: their role in autoimmune inflammation, Acta Nat., 2016, vol. 8, no. 1(28), pp. 23—36.

  14. 14

    Khal’chinskii, S.E., Komov, V.P., Nasyrova, R.F., and Ivanov, M.V., Dysregulation of miRNA in mental and neurological disorders, Obozr. Psikhiatr. Med. Psikhol., 2014, no. 4, pp. 23—29.

  15. 15

    Brase, J.C., Johannes, M., Schlomm, T., et al., Circulating miRNAs are correlated with tumor progression in prostate cancer, Int. J. Cancer, 2011, vol. 128, no. 3, pp. 608—616. https://doi.org/10.1002/ijc.25376

  16. 16

    Heneghan, H.M., Miller, N., Lowery, A.J., et al., Circulating microRNAs as novel minimally invasive biomarkers for breast cancer, Ann. Surg., 2010, vol. 251, no. 3, pp. 499—505. https://doi.org/10.1097/SLA.0b013e3181cc939f

  17. 17

    Mouillet, J.F., Ouyang, Y., Coyne, C.B., and Sadovsky, Y., MicroRNAs in placental health and disease, Am. J. Obstet. Gynecol., 2015, vol. 213, no. 4, suppl., pp. S163—S172. https://doi.org/10.1016/j.ajog.2015.05.057

  18. 18

    D’Alessandra, Y., Devanna, P., Limana, F., et al., Circulating microRNAs are new and sensitive biomarkers of myocardial infarction, Eur. Heart J., 2010, vol. 31, no. 22, pp. 2765—2773. https://doi.org/10.1093/eurheartj/ehq167

  19. 19

    Wang, G.K., Zhu, J.Q., Zhang, J.T., et al., Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans, Eur. Heart J., 2010, vol. 31, no. 6, pp. 659—666. https://doi.org/10.1093/eurheartj/ehq013

  20. 20

    Miura, K., Miura, S., Yamasaki, K., et al., Identification of pregnancy-associated microRNAs in maternal plasma, Clin. Chem., 2010, vol. 56, no. 11, pp. 1767—1771. https://doi.org/10.1373/clinchem.2010.147660

  21. 21

    Gu, Y., Sun, J., Groome, L.J., and Wang, Y., Differential miRNA expression profiles between the first and third trimester human placentas, Am. J. Physiol. Endocrinol. Metab., 2013, vol. 304, no. 8, pp. E836—E843. https://doi.org/10.1152/ajpendo.00660.2012

  22. 22

    Cai, M., Kolluru, G.K., and Ahmed, A., Small molecule, big prospects: microRNA in pregnancy and its complications, J. Pregnancy, 2017, vol. 2017, article ID 6972732. https://doi.org/10.1155/2017/6972732

  23. 23

    Zhao, Z., Moley, K.H., and Gronowski, A.M., Diagnostic potential for miRNAs as biomarkers for pregnancy-specific diseases, Clin. Biochem., 2013, vol. 46, nos. 10—11, pp. 953—960. https://doi.org/10.1016/j.clinbiochem.2013.01.026

  24. 24

    Chim, S.S., Shing, T.K., Hung, E.C., et al., Detection and characterization of placental microRNAs in maternal plasma, Clin. Chem., 2008, vol. 54, no. 3, pp. 482—490. https://doi.org/10.1373/clinchem.2007.097972

  25. 25

    Gilad, S., Meiri, E., Yogev, Y., et al., Serum microRNAs are promising novel biomarkers, PLoS One, 2008, vol. 3, no. 9, article ID e3148. https://doi.org/10.1371/journal.pone.0003148

  26. 26

    Kotlabova, K., Doucha, J., and Hromadnikova, I., Placental-specific microRNA in maternal circulation-identification of appropriate pregnancy-associated microRNAs with diagnostic potential, J. Reprod. Immunol., 2011, vol. 89, no. 2, pp. 185—191. https://doi.org/10.1016/j.jri.2011.02.006

  27. 27

    Hromadnikova, I., Kotlabova, K., Doucha, J., et al., Absolute and relative quantification of placenta-specific microRNAs in maternal circulation with placental insufficiency-related complications, J. Mol. Diagn., 2012, vol. 14, no. 2, pp. 160—167. https://doi.org/10.1016/j.jmoldx.2011.11.003

  28. 28

    Zhao, G., Zhou, X., Chen, S., et al., Differential expression of microRNAs in deciduas-derived mesenchymal stem cells from patients with preeclampsia, J. Biomed. Sci., 2014, vol. 21, no. 1, article ID 81. https://doi.org/10.1186/s12929-014-0081-3

  29. 29

    Zhou, C., Zou, Q., Li, H., et al., Preeclampsia downregulates microRNAs in fetal endothelial cells: roles of miR-29a/c-3p in endothelial function, J. Clin. Endocrinol. Metab., 2017, vol. 102, no. 9, pp. 3470—3479. https://doi.org/10.1210/jc.2017-00849

  30. 30

    Harapan, H. and Andalas, M., The role of microRNAs in the proliferation, differentiation, invasion, and apoptosis of trophoblasts during the occurrence of preeclampsia—a systematic review, Tzu Chi Med. J., 2015, vol. 27, no. 2, pp. 54—64. https://doi.org/10.1016/j.tcmj.2015.05.001

  31. 31

    Harapan, H. and Yeni, C.M., The role of microRNAs on angiogenesis and vascular pressure in preeclampsia: the evidence from systematic review, Egypt. J. Med. Hum. Genet., 2015, vol. 16, no. 4, pp. 313—325. https://doi.org/10.1016/j.ejmhg.2015.03.006

  32. 32

    Li, Q., Long, A., Jiang, L., et al., Quantification of preeclampsia-related microRNAs in maternal serum, Biomed. Rep., 2015, vol. 3, no. 6, pp. 792—796.

  33. 33

    Munaut, C., Tebache, L., Blacher, S., et al., Dysregulated circulating miRNAs in preeclampsia, Biomed. Rep., 2016, vol. 5, no. 6, pp. 686—692. https://doi.org/10.3892/br.2016.779

  34. 34

    Timofeeva, A.V., Gusar, V.A., Kan, N.E., et al., Identification of potential early biomarkers of preeclampsia, Placenta, 2018, vol. 61, pp. 61—71. https://doi.org/10.1016/j.placenta.2017.11.011

  35. 35

    Sheikh, A.M., Small, H.Y., Currie, G., Dellis, C., et al., Systematic review of micro-RNA expression in pre-eclampsia identifies a number of common pathways associated with the disease, PLoS One, 2016, vol. 11, no. 8, article ID e0160808. https://doi.org/10.1371/journal.pone.0160808

  36. 36

    Pineles, B.L., Romero, R., Montenegro, D., et al., Distinct subsets of microRNAs are expressed differentially in the human placentas of patients with preeclampsia, Am. J. Obstet. Gynecol., 2007, vol. 196, no. 3, pp. 261.e1—261.e6.

  37. 37

    Hu, Y., Li, P., Hao, S., et al., Differential expression of microRNAs in the placentae of Chinese patients with severe preeclampsia, Clin. Chem. Lab Med., 2009, vol. 47, no. 8, pp. 923—929. https://doi.org/10.1515/CCLM.2009.228

  38. 38

    Zhu, X.M., Han, T., Sargent, I.L., et al., Differential expression profile of microRNAs in human placentas from preeclamptic pregnancies vs. normal pregnancies, Am. J. Obstet. Gynecol., 2009, vol. 200, no. 6, pp. 661.e1—661.e7. https://doi.org/10.1016/j.ajog.2008.12.045

  39. 39

    Enquobahrie, D.A., Abetew, D.F., Sorensen, T.K., et al., Placental microRNA expression in pregnancies complicated by preeclampsia, Am. J. Obstet. Gynecol., 2011, vol. 204, no. 2, pp. 178.e12—178.e21. https://doi.org/10.1016/j.ajog.2010.09.004

  40. 40

    Mayor-Lynn, K., Toloubeydokhti, T., Cruz, A.C., and Chegini, N., Expression profile of microRNAs and mRNAs in human placentas from pregnancies complicated by preeclampsia and preterm labor, Reprod. Sci., 2011, vol. 18, no. 1, pp. 46—56. https://doi.org/10.1177/1933719110374115

  41. 41

    Noack, F., Ribbat-Idel, J., Thorns, C., et al., MiRNA expression profiling in formalin-fixed and paraffin-embedded placental tissue samples from pregnancies with severe preeclampsia, J. Perinat. Med., 2011, vol. 39, no. 3, pp. 267—271. https://doi.org/10.1515/JPM.2011.012

  42. 42

    Ishibashi, O., Ohkuchi, A., Ali, M.M., et al., Hydroxysteroid (17-β) dehydrogenase 1 is dysregulated by miR-210 and miR-518c that are aberrantly expressed in preeclamptic placentas: a novel marker for predicting preeclampsia, Hypertension, 2012, vol. 59, no. 2, pp. 265—273. https://doi.org/10.1161/HYPERTENSIONAHA.111.180232

  43. 43

    Wang, W., Feng, L., Zhang, H., et al., 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., 2012, vol. 97, no. 6, pp. E1051—E1059. https://doi.org/10.1210/jc.2011-3131

  44. 44

    Betoni, J.S., Derr, K., Pahl, M.C., et al., MicroRNA analysis in placentas from patients with preeclampsia: comparison of new and published results, Hypertens. Pregnancy, 2013, vol. 32, no. 4, pp. 321—339. https://doi.org/10.3109/10641955.2013.807819

  45. 45

    Choi, S.Y., Yun, J., Lee, O.J., et al., MicroRNA expression profiles in placenta with severe preeclampsia using a PNA-based microarray, Placenta, 2013, vol. 34, no. 9, pp. 799—804. https://doi.org/10.1016/j.placenta.2013.06.006

  46. 46

    Xu, P., Zhao, Y., Liu, M., et al., Variations of microRNAs in human placentas and plasma from preeclamptic pregnancy, Hypertension, 2014, vol. 63, no. 6, pp. 1276—1284. https://doi.org/10.1161/HYPERTENSIONAHA.113.02647

  47. 47

    Weedon-Fekjær, M.S., Sheng, Y., Sugulle, M., et al., Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely correlated with maternal circulating leptin, Placenta, 2014, vol. 35, no. 9, pp. 709—717. https://doi.org/10.1016/j.placenta.2014.07.002

  48. 48

    Jiang, F., Li, J., Wu, G., et al., Upregulation of microRNA-335 and microRNA-584 contributes to the pathogenesis of severe preeclampsia through downregulation of endothelial nitric oxide synthase, Mol. Med. Rep., 2015, vol. 12, pp. 5383—5390. https://doi.org/10.3892/mmr.2015.4018

  49. 49

    Zhang, C., Li, Q., Ren, N., et al., Placental miR-106a∼ 363 cluster is dysregulated in preeclamptic placenta, Placenta, 2015, vol. 36, no. 2, pp. 250—252. https://doi.org/10.1016/j.placenta.2014.11.020

  50. 50

    Yang, S., Li, H., Ge, Q., et al., Deregulated microRNA species in the plasma and placenta of patients with preeclampsia, Mol. Med. Rep., 2015, vol. 12, no. 1, pp. 527—534. https://doi.org/10.3892/mmr.2015.3414

  51. 51

    Vashukova, E.S., Glotov, A.S., Fedotov, P.V., et al., Placental microRNA expression in pregnancies complicated by superimposed pre-eclampsia on chronic hypertension, Mol. Med. Rep., 2016, vol. 14, no. 1, pp. 22—32. https://doi.org/10.3892/mmr.2016.5268

  52. 52

    Gunel, T., Hosseini, M.K., Gumusoglu, E., et al., Expression profiling of maternal plasma and placenta microRNAs in preeclamptic pregnancies by microarray technology, Placenta, 2017, vol. 52, pp. 77—85. https://doi.org/10.1016/j.placenta.2017.02.019

  53. 53

    Lykoudi, A., Kolialexi, A., Lambrou, G.I., et al., Dysregulated placental microRNAs in early and late onset preeclampsia, Placenta, 2018, vol. 61, pp. 24—32. https://doi.org/10.1016/j.placenta.2017.11.005

  54. 54

    Yang, Q., Lu, J., Wang, S., et al., Application of next-generation sequencing technology to profile the circulating microRNAs in the serum of preeclampsia versus normal pregnant women, Clin. Chim. Acta, 2011, vol. 412, nos. 23—24, pp. 2167—2173. https://doi.org/10.1016/j.cca.2011.07.029

  55. 55

    Ura, B., Feriotto, G., Monasta, L., et al., Potential role of circulating microRNAs as early markers of preeclampsia, Taiwan J. Obstet. Gynecol., 2014, vol. 53, no. 2, pp. 232—234. https://doi.org/10.1016/j.tjog.2014.03.001

  56. 56

    Wu, L., Zhou, H., Lin, H., et al., Circulating microRNAs are elevated in plasma from severe preeclamptic pregnancies, Reproduction, 2012, vol. 143, no. 3, pp. 389—397. https://doi.org/10.1530/REP-11-0304

  57. 57

    Li, H., Ge, Q., Guo, L., and Lu, Z., Maternal plasma miRNAs expression in preeclamptic pregnancies, Biomed. Res. Int., 2013, article ID 970265. https://doi.org/10.1155/2013/970265

  58. 58

    Luque, A., Farwati, A., Crovetto, F., et al., Usefulness of circulating microRNAs for the prediction of early preeclampsia at first-trimester of pregnancy, Sci. Rep., 2014, vol. 4, article 4882. https://doi.org/10.1038/srep04882

  59. 59

    Luque, A., Farwati, A., Crovetto, F., et al., Differential expression of microRNA-206 and its target genes in preeclampsia, J. Hypertens., 2015, vol. 33, pp. 2068—2074. https://doi.org/10.1097/HJH.0000000000000656

  60. 60

    Murphy, M.S., Casselman, R.C., Tayade, C., and Smith, G.N., Differential expression of plasma microRNA in preeclamptic patients at delivery and 1 year postpartum, Am. J. Obstet. Gynecol., 2015, vol. 213, no. 3, pp. 367.e1—367.e9.

  61. 61

    Sandrim, V., Luizon, M., Palei, A., et al., Circulating microRNA expression profiles in preeclampsia: evidence of increased miR-885-5p levels, BJOG, 2016, vol. 123, no. 13, pp. 2120—2128. https://doi.org/10.1111/1471-0528.13903

  62. 62

    Jairajpuri, D.S., Malalla, Z.H., Mahmood, N., and Almawi, W.Y., Circulating microRNA expression as predictor of preeclampsia and its severity, Gene, 2017, vol. 627, pp. 543—548. https://doi.org/10.1016/j.gene.2017.07.010

  63. 63

    Yoffe, L., Gilam, A., Yaron, O., et al., Early detection of preeclampsia using circulating small non-coding RNA, Sci. Rep., 2018, vol. 8, no. 1, pp. 1—11. https://doi.org/10.1038/s41598-018-21604-6

  64. 64

    Zhang, Y., Fei, M., Xue, G., et al., Elevated levels of hypoxia-inducible microRNA-210 in pre-eclampsia: new insights into molecular mechanisms for the disease, J. Cell Mol. Med., 2012, vol. 16, no. 2, pp. 249—259. https://doi.org/10.1111/j.1582-4934.2011.01291.x

  65. 65

    Luo, R., Shao, X., Xu, P., et al., MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1, Hypertension, 2014, vol. 64, no. 4, pp. 839—845. https://doi.org/10.1161/HYPERTENSIONAHA.114.03530

  66. 66

    Lee, D.C., Romero, R., Kim, J.S., et al., MiR-210 targets iron—sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies, Am. J. Pathol., 2011, vol. 179, no. 2, pp. 590—602. https://doi.org/10.1016/j.ajpath.2011.04.035

  67. 67

    Luo, R., Wang, Y., Xu, P., et al., Hypoxia-inducible miR-210 contributes to preeclampsia via targeting thrombospondin type I domain containing 7A, Sci. Rep., 2016, vol. 6, article 19588. https://doi.org/10.1038/srep19588

  68. 68

    Kopriva, S.E., Chiasson, V.L., Mitchell, B.M., et al., Chatterjee P.TLR3-induced placental miR-210 down-regulates the STAT6/interleukin-4 pathway, PLoS One, 2013, vol. 8, no. 7, article ID e67760. https://doi.org/10.1371/journal.pone.0067760

  69. 69

    Meng, H.-X., Xu, L.-N., Jing, G., et al., MiR-223 promotes trophoblast cell survival and invasion by targeting STAT3 in preeclampsia, Int. J. Clin. Exp. Med., 2017, vol. 10, no. 4, pp. 6577—6585.

  70. 70

    Dominguez, F., Moreno-Moya, J.M., Lozoya, T., et al., Embryonic miRNA profiles of normal and ectopic pregnancies, PLoS One, 2014, vol. 9, no. 7, article ID e102185. https://doi.org/10.1371/journal.pone.0102185

  71. 71

    Tabet, F., Vickers, K.C., Cuesta Torres, L.F., et al., HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells, Nat. Commun., 2014, vol. 5, article ID 3292. https://doi.org/10.1038/ncomms4292

  72. 72

    Zhao, Y., Li, D., Chen, D., et al., Increased miR-223 expression promotes proliferation and migration of retinal endothelial cells and pathogenesis of diabetic retinopathy by targeting EIF4E3 and IGF-1R, Int. J. Clin. Exp. Pathol., 2017, vol. 10, no. 3, pp. 2950—2959.

  73. 73

    Zhu, X., Yang, Y., Han, T., et al., Suppression of microRNA-18a expression inhibits invasion and promotes apoptosis of human trophoblast cells by targeting the estrogen receptor α gene, Mol. Med. Rep., 2015, vol. 12, no. 2, pp. 2701—2706. https://doi.org/10.3892/mmr.2015.3724

  74. 74

    Yang, Y., Zhang, S., Li, Y., et al., Inhibition of miR-18a increases expression of estrogen receptor 1 and promotes apoptosis in human HTR8 trophoblasts, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2017, vol. 33, no. 8, pp. 1102—1107.

  75. 75

    Han, F., Wu, Y., and Jiang, W., MicroRNA-18a decreases choroidal endothelial cell proliferation and migration by inhibiting HIF1A expression, Med. Sci. Monit., 2015, vol. 5, no. 21, pp. 1642—1647. https://doi.org/10.12659/MSM.893068

  76. 76

    Wu, L., Song, W.Y., Xie, Y., et al., miR-181a-5p suppresses invasion and migration of HTR-8/SVneo cells by directly targeting IGF2BP2,Cell Death Dis., 2018, vol. 9, no. 2, article ID 16. https://doi.org/10.1038/s41419-017-0045-0

  77. 77

    Yan, X., Tan, Y., Yuan, Y., et al., Upregulation of miR-181a-5p represses VEGF pathway in high glucose treated human retinal endothelial cells, Int. J. Clin. Exp. Med., 2016, vol. 9, no. 2, pp. 2493—2499.

  78. 78

    Kazenwadel, J., Michael, M.Z., and Harvey, N.L., Prox1 expression is negatively regulated by miR-181 in endothelial cells, Blood, 2010, vol. 116, no. 13, pp. 2395—2401. https://doi.org/10.1182/blood-2009-12-256297

  79. 79

    Chaiwangyen, W., Ospina-Prieto, S., Photini, S.M., et al., Dissimilar microRNA-21 functions and targets in trophoblastic cell lines of different origin, Int. J. Biochem. Cell Biol., 2015, vol. 68, pp. 187—196. https://doi.org/10.1016/j.biocel.2015.08.018

  80. 80

    Gu, Y., Bian, Y., Xu, X., et al., Downregulation of miR-29a/b/c in placenta accreta inhibits apoptosis of implantation site intermediate trophoblast cells by targeting MCL1, Placenta, 2016, vol. 48, pp. 13—19. https://doi.org/10.1016/j.placenta.2016.09.017

  81. 81

    Yang, Z., Wu, L., Zhu, X., et al., MiR-29a modulates the angiogenic properties of human endothelial cells, Biochem. Biophys. Res. Commun., 2013, vol. 434, no. 1, pp. 143—149. https://doi.org/10.1016/j.bbrc.2013.03.054

  82. 82

    Wang, J., Wang, Y., Wang, Y., et al., Transforming growth factor β-regulated microRNA-29a promotes angiogenesis through targeting the phosphatase and tensin homolog in endothelium, J. Biol. Chem., 2013, vol. 288, no. 15, pp. 10418—10426. https://doi.org/10.1074/jbc.M112.444463

  83. 83

    Schober, A., Nazari-Jahantigh, M., Wei, Y., et al., MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1, Nat. Med., 2014, vol. 20, no. 13, pp. 368—376. https://doi.org/10.1038/nm.3487

  84. 84

    Anton, L., Olarerin-George, A.O., Hogenesch, J.B., et al., Placental expression of miR-517a/b and miR-517c contributes to trophoblast dysfunction and preeclampsia, PLoS One, 2015, vol. 10, no. 3, article ID e0122707. https://doi.org/10.1371/journal.pone.0122707

  85. 85

    Liu, M., Wang, Y., Lu, H., et al., MiR-518b enhances human trophoblast cell proliferation through targeting Rap1b and activating Ras-MAPK signal, Front. Endocrinol. (Lausanne), 2018, vol. 9, article 100. https://doi.org/10.3389/fendo.2018.00100

  86. 86

    Fish, J.E., Santoro, M.M., Morton, S.U., et al., MiR-126 regulates angiogenic signaling and vascular integrity, Dev. Cell, 2008, vol. 15, no. 2, pp. 272—284. https://doi.org/10.1016/j.devcel.2008.07.008

  87. 87

    Hong, F., Li, Y., and Xu, Y., Decreased placental miR-126 expression and vascular endothelial growth factor levels in patients with pre-eclampsia, J. Int. Med. Res., 2014, vol. 42, no. 6, pp. 1243—1251. https://doi.org/10.1177/0300060514540627

  88. 88

    van Solingen, C., de Boer, H.C., Bijkerk, R., et al., MicroRNA-126 modulates endothelial SDF-1 expression and mobilization of Sca-1(+)/Lin(–) progenitor cells in ischaemia, Cardiovasc. Res., 2011, vol. 92, no. 3, pp. 449—455. https://doi.org/10.1093/cvr/cvr227

  89. 89

    Urbich, C., Kaluza, D., Frömel, T., et al., MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A, Blood, 2012, vol. 119, no. 6, pp. 1607—1616. https://doi.org/10.1182/blood-2011-08-373886

  90. 90

    Chen, Y. and Gorski, D.H., Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5,Blood, 2008, vol. 111, no. 3, pp. 1217—1226.

  91. 91

    Fan, A., Wang, Q., Yuan, Y., et al., Liver X receptor-α and miR-130a-3p regulate expression of sphingosine 1-phosphate receptor 2 in human umbilical vein endothelial cells, Am. J. Physiol.: Cell Physiol., 2016, vol. 310, no. 3, pp. C216—C226. https://doi.org/10.1152/ajpcell.00102.2015

  92. 92

    Zhu, X.M., Han, T., Wang, X.H., et al., Overexpression of miR-152 leads to reduced expression of human leukocyte antigen-G and increased natural killer cell mediated cytolysis in JEG-3 cells, Am. J. Obstet. Gynecol., 2010, vol. 202, no. 6, pp. 592.e1—592.e7. https://doi.org/10.1016/j.ajog.2010.03.002

  93. 93

    Cai, M., Wang, K., and Ahmed, A., Preeclampsia, Pub, no. WO/2016/151287. Int. Appl., no. PCT/GB2016/050710, 2016.

  94. 94

    Bai, Y., Yang, W., Yang, H.X., et al., Downregulated miR-195 detected in preeclamptic placenta affects trophoblast cell invasion via modulating ActRIIA expression, PLoS One, 2012, vol. 7, no. 6, article ID e38875. https://doi.org/10.1371/journal.pone.0038875

  95. 95

    Sandrim, V.C., Dias, M.C., Bovolato, A.L., et al., Plasma from pre-eclamptic patients induces the expression of the anti-angiogenic miR-195-5p in endothelial cells, J. Cell. Mol. Med., 2016, vol. 20, no. 6, pp. 1198—2000. https://doi.org/10.1111/jcmm.12767

  96. 96

    Yuan, M., Yuan, H., Zhou, C., et al., The significance of low plasma miR-335 level in patients with acute cerebral infarction may be associated with the loss of control of CALM1 expression, Int. J. Clin. Exp. Med., 2016, vol. 9, no. 10, pp. 19595—19601.

  97. 97

    Ding, J., Huang, F., Wu, G., et al., MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2,PLoS One, 2015, vol. 10, no. 3, article ID e0120321. https://doi.org/10.1371/journal.pone.0120321

  98. 98

    Xie, L., Mouillet, J.F., Chu, T., et al., C19MC microRNAs regulate the migration of human trophoblasts, Endocrinology, 2014, vol. 155, no. 12, pp. 4975—4985. https://doi.org/10.1210/en.2014-1501

  99. 99

    Tannetta, D. and Sargent, I., Placental disease and the maternal syndrome of preeclampsia: missing links?, Curr. Hypertens. Rep., 2013, vol. 15, no. 6, pp. 590—599. https://doi.org/10.1007/s11906-013-0395-7

  100. 100

    Ailamazyan, E.K., Stepanova, O.I., Sel’kov, S.A., and Sokolov, D.I., Maternal immune cells and trophoblasts: “constructive cooperation” towards a common goal, Vestn. Ross. Akad. Med. Nauk, 2013, vol. 68, no. 11, pp. 12—21. https://doi.org/10.15690/vramn.v68i11.837

  101. 101

    Sokolov, D.I., Vasculogenesis and angiogenesis in the development of placenta, Zh. Akush. Zhen. Bolezn., 2007, vol. 56, no. 3, pp. 129—133.

  102. 102

    Mütze, S., Rudnik-Schöneborn, S., Zerres, K., and Rath, W., Genes and the preeclampsia syndrome, J. Perinat. Med., 2008, vol. 36, no. 1, pp. 38—58.

  103. 103

    Choi, J.W., Im, M.W., and Pai, S.H., Nitric oxide production increases during normal pregnancy and decreases in preeclampsia, Ann. Clin. Lab. Sci., 2002, vol. 32, no. 3, pp. 257—263.

  104. 104

    Camps, C., Buffa, F.M., Colella, S., et al., Hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer, Clin. Cancer Res., 2008, vol. 14, no. 5, pp. 1340—1348. https://doi.org/10.1158/1078-0432.CCR-07-1755

  105. 105

    Chan, S.Y. and Loscalzo, J., MicroRNA-210: a unique and pleiotropic hypoxamir, Cell Cycle. 2010, vol. 9, no. 6, pp. 1072—1083.

  106. 106

    Ohkuchi, A., Ishibashi, O., Hirashima, C., et al., Plasma level of hydroxysteroid (17-β) dehydrogenase 1 in the second trimester is an independent risk factor for predicting preeclampsia after adjusting for the effects of mean blood pressure, bilateral notching and plasma level of soluble fms-like tyrosine kinase 1/placental growth factor ratio, Hypertens. Res., 2012, vol. 35, no. 12, pp. 1152—1158. https://doi.org/10.1038/hr.2012.109

Download references


The study was conducted with the financial support of the topic of fundamental scientific research no. 0558-2017-0056.

Author information

Correspondence to E. S. Vashukova.

Ethics declarations

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

Additional information

Translated by I. Grishina

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vashukova, E.S., Glotov, A.S. & Baranov, V.S. MicroRNAs Associated with Preeclampsia. Russ J Genet 56, 1–16 (2020). https://doi.org/10.1134/S1022795419080167

Download citation


  • miRNA
  • pregnancy
  • preeclampsia
  • biomarkers