Skip to main content

Advertisement

SpringerLink
Log in

MiR-203 Participates in Human Placental Angiogenesis by Inhibiting VEGFA and VEGFR2 Expression

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Angiogenesis during placentation is of great significance in maintaining normal pregnancy. However, the molecular mechanisms of this process are not clear. It has been reported that miR-203 plays a critical role in the development and progression of many tumors but not focused on the relationship between miR-203 and placental angiogenesis. The present study aims to illustrate the correlation between miR-203 and vascular endothelial growth factor (VEGFA)/vascular endothelial growth factor receptors 2 (VEGFR2) in human placenta and human umbilical vein endothelial cells (HUVECs) obtained from 40 samples. Samples of human placenta were collected based on gestation age, which was divided into early preterm (n=10), late preterm (n=12), and term (n = 18). In this work, we demonstrated that the expression of miR-203 decreased significantly in the placenta according to the gestation age, in contrast, the expression of VEGFA and VEGFR2 increased accordingly. In vitro experiments revealed that overexpression of miR-203 not only suppressed the proliferation, migration, invasion, and tube formation of HUVECs but also affected the expression of VEGFA and VEGFR2. Furthermore, inhibition of miR-203 expression showed equally apparent positive effects on HUVECs. In conclusion, our study suggests that miR-203 plays an important role in regulating placental angiogenesis through inhibiting the expression of VEGFA and VEGFR2, thus miR-203 may represent a potential therapeutic target for patients with abnormal formation of blood vessels in the placenta.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Avagliano L, Garo C, Marconi AM. Placental amino acids transport in intrauterine growth restriction. J Pregnancy. 2012;2012: 972562.

    PubMed  PubMed Central  Google Scholar 

  2. Wulff C, Weigand M, Kreienberg R, Fraser HM. Angiogenesis during primate placentation in health and disease. Reproduction. 2003;126(5):569–577.

    CAS  PubMed  Google Scholar 

  3. Williams PJ, Bulmer JN, Innes BA, Broughton Pipkin F. Possible roles for folic acid in the regulation of trophoblast invasion and placental development in normal early human pregnancy. Biol Reprod. 2011;84(6):1148–1153.

    CAS  PubMed  Google Scholar 

  4. Iruela-Arispe ML, Dvorak HF. Angiogenesis: a dynamic balance of stimulators and inhibitors. Thromb Haemost. 1997;78(1): 672–677.

    CAS  PubMed  Google Scholar 

  5. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N. Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 1989;246(4935):1306–1309.

    CAS  PubMed  Google Scholar 

  6. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling—in control of vascular function. Nat Rev Mol Cell Biol. 2006;7(5):359–371.

    CAS  PubMed  Google Scholar 

  7. Li W, Huang H, Su J, et al. miR-124 acts as a tumor suppressor in glioblastoma via the inhibition of signal transducer and activator of transcription 3. Mol Neurobiol. 2017;54(4): 2555–2561.

    CAS  PubMed  Google Scholar 

  8. He Y, Zhao C, Liu Y, et al. MiR-124 functions as a tumor suppressor via targeting hCLOCK1 in glioblastoma. Mol Neurobiol. 2017;54(3):2375.

    CAS  PubMed  Google Scholar 

  9. Kagiya T. MicroRNAs and osteolytic bone metastasis: the roles of microRNAs in tumor-induced osteoclast differentiation. J Clin Med. 2015;4(9):1741–1752.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Park JH, Shin C. MicroRNA-directed cleavage of targets: mechanism and experimental approaches. BMB Rep. 2014;47(8):417–423.

    PubMed  PubMed Central  Google Scholar 

  11. Macfarlane LA, Murphy PR. MicroRNA: biogenesis, function and role in cancer. Curr Genomics. 2010;11(7):537–561.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Farazi TA, Hoell JI, Morozov P, Tuschl T. MicroRNAs in human cancer. Adv Exp Med Biol. 2013;774:1–20.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Li Z, Li N, Wu M, et al. Expression of miR-126 suppresses migration and invasion of colon cancer cells by targeting CXCR4. Mol CellBiochem. 2013;381(1-2):233–242.

    CAS  Google Scholar 

  14. Png KJ, Halberg N, Yoshida M, Tavazoie SF. A microRNA regulon that mediates endothelial recruitment and metastasis by cancer cells. Nature. 2011;481(7380):190–194.

    PubMed  Google Scholar 

  15. Wu YY, Chen YL, Jao YC, et al. miR-320 regulates tumor angiogenesis driven by vascular endothelial cells in oral cancer by silencing neuropilin 1. Angiogenesis. 2014;17(1): 247–260.

    CAS  PubMed  Google Scholar 

  16. Kong W, He L, Richards EJ, et al. Upregulation of miRNA-155 promotes tumour angiogenesis by targeting VHL and is associated with poor prognosis and triple-negative breast cancer. Oncogene. 2014;33(6):679–689.

    CAS  PubMed  Google Scholar 

  17. Ye J, Wu X, Wu D, et al. miRNA-27b targets vascular endothelial growth factor C to inhibit tumor progression and angiogenesis in colorectal cancer. PLoS One. 2013;8(4):e60687.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tu Y, Liu L, Zhao D, et al. Overexpression of miRNA-497 inhibits tumor angiogenesis by targeting VEGFR2. Sci Rep. 2015;5: 13827.

    PubMed  PubMed Central  Google Scholar 

  19. Pecot CV, Rupaimoole R, Yang D, et al. Tumour angiogenesis regulation by the miR-200 family. Nat Commun. 2013;4: 2427.

    PubMed  PubMed Central  Google Scholar 

  20. Nelissen EC, Dumoulin JC, Busato F, et al. Altered gene expression in human placentas after IVF/ICSI. Hum Reprod. 2014;29(12):2821–2831.

    CAS  PubMed  Google Scholar 

  21. Trang P, Wiggins JF, Daige CL, et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol Ther. 2011;19(6):1116–1122.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin Z, Zhang Q, Luo W. Angiogenesis inhibitors as therapeutic agents in cancer: challenges and future directions. Eur J Pharmacol. 2016;793:76–81.

    CAS  PubMed  Google Scholar 

  23. Icli B, Nabzdyk CS, Lujan-Hernandez J, et al. Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a. J Mol Cell Cardiol. 2016;91:151–159.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Zhu X, Er K, Mao C, et al. miR-203 suppresses tumor growth and angiogenesis by targeting VEGFA in cervical cancer. Cell Physiol Biochem. 2013;32(1):64–73.

    CAS  PubMed  Google Scholar 

  25. Xu L, Shen B, Chen T, Dong P. miR-203 is involved in the laryngeal carcinoma pathogenesis via targeting VEGFA and Cox-2. Onco Targets Ther. 2016;9:4629–4637.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Di Stefano V, Wang B, Parobchak N, Roche N, Rosen T. RelB/p52-mediated NF-kappaB signaling alters histone acetylation to increase the abundance of corticotropin-releasing hormone in human placenta. Sci Signal. 2015;8(391):ra85.

    PubMed  Google Scholar 

  27. Ross CA. The trophoblast model of cancer. Nutr Cancer. 2015;67(1):61–67.

    CAS  PubMed  Google Scholar 

  28. Poole TJ, Coffin JD. Vasculogenesis and angiogenesis: two distinct morphogenetic mechanisms establish embryonic vascular pattern. J Exp Zool. 1989;251(2):224–231.

    CAS  PubMed  Google Scholar 

  29. Folkman J, Klagsbrun M. Angiogenic factors. Science. 1987;235(4787):442–447.

    CAS  PubMed  Google Scholar 

  30. Zygmunt M, Herr F, Munstedt K, Lang U, Liang OD. Angiogenesis and vasculogenesis in pregnancy. Eur J Obstet Gynecol ReprodBiol. 2003;110(suppl 1):S10–S18.

    CAS  Google Scholar 

  31. Schiessl B, Innes BA, Bulmer JN, et al. Localization of angiogenic growth factors and their receptors in the human placental bed throughout normal human pregnancy. Placenta. 2009;30(1):79–87.

    CAS  PubMed  Google Scholar 

  32. Darling AM, McDonald CR, Conroy AL, et al. Angiogenic and inflammatory biomarkers in midpregnancy and small-for-gestational-age outcomes in Tanzania. Am J Obstet Gynecol. 2014;211(5):509.e501-e508.

    PubMed  PubMed Central  Google Scholar 

  33. Nagamatsu T, Fujii T, Kusumi M, et al. Cytotrophoblasts up-regulate soluble FMS-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia. Endocrinology. 2004;145(11):4838–4845.

    CAS  PubMed  Google Scholar 

  34. Bo J, Yang G, Huo K, et al. microRNA-203 suppresses bladder cancer development by repressing BCL-W expression. FEBS J. 2011;278(5):786–792.

    CAS  PubMed  Google Scholar 

  35. Wang C, Zheng X, Shen C, Shi Y. MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells. J Exp Clin Cancer Res. 2012;31:58.

    PubMed  PubMed Central  Google Scholar 

  36. Viticchie G, Lena AM, Latina A, et al. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle. 2011;10(7):1121–1131.

    CAS  PubMed  Google Scholar 

  37. Furuta M, Kozaki KI, Tanaka S, et al. miR-124 and miR-203 are epigenetically silenced tumor-suppressive microRNAs in hepatocellular carcinoma. Carcinogenesis. 2010;31(5):766–776.

    CAS  PubMed  Google Scholar 

  38. Wu SQ, Niu WY, Li YP, Huang HB, Zhan R. miR-203 inhibits cell growth and regulates G1/S transition by targeting Bmi-1 in myeloma cells. Mol Med Rep. 2016;14(5):4795–4801.

    CAS  PubMed  Google Scholar 

  39. Zhou P, Jiang N, Zhang GX, Sun Q. MiR-203 inhibits tumor invasion and metastasis in gastric cancer by ATM. Acta Biochim Biophys Sin (Shanghai). 2016;48(8):696–703.

    CAS  Google Scholar 

  40. Liu Y, Gao S, Chen X, et al. Overexpression of miR-203 sensitizes paclitaxel (Taxol)-resistant colorectal cancer cells through targeting the salt-inducible kinase 2 (SIK2). Tumour Biol. 2016;37(9):12231–12239.

    CAS  PubMed  Google Scholar 

  41. Chamorro-Jorganes A, Araldi E, Penalva LO, et al. MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arterioscler Thromb Vasc Biol. 2011;31(11):2595–2606.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Wurdinger T, Tannous BA, Saydam O, et al. miR-296 regulates growth factor receptor overexpression in angiogenic endothelial cells. Cancer Cell. 2008;14(5):382–393.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The First Department of Gynaecology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan 430060, Hubei, China

    Fulin Liu MM, Wanrong Wu MM, Yurou Chen MM, Hanshu Wu MM & Wei Zhang MD

  2. Department of Gynaecology, Zhongnan Hospital of Wuhan University, Wuchang District, China

    Kejia Wu MD

  3. Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China

    Hui Wang MD

  4. Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan, China

    Hui Wang MD & Wei Zhang MD

Authors
  1. Fulin Liu MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanrong Wu MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kejia Wu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yurou Chen MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hanshu Wu MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hui Wang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Zhang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Zhang MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, F., Wu, W., Wu, K. et al. MiR-203 Participates in Human Placental Angiogenesis by Inhibiting VEGFA and VEGFR2 Expression. Reprod. Sci. 25, 358–365 (2018). https://doi.org/10.1177/1933719117725817

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719117725817

Keywords

Search

Navigation