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Hossein Razi, M., Eftekhar, M., Ghasemi, N., Hasan Sheikhha, M., & Dehghani Firoozabadi, A. (2020). Expression levels of circulatory mir-185-5p, vascular endothelial growth factor, and platelet-derived growth factor target genes in endometriosis. International Journal of Reproductive BioMedicine (IJRM), 13(5), 347–358. https://doi.org/10.18502/ijrm.v13i5.7155
https://doi.org/10.18502/ijrm.v13i5.7155
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Mohammad Hossein Razi
Mohammad Hossein Razi
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Maryam Eftekhar
Maryam Eftekhar
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Nasrin Ghasemi
Nasrin Ghasemi
Abortion Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Mohammad Hasan Sheikhha
Mohammad Hasan Sheikhha
Research and Clinical Center for Infertility, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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Ali Dehghani Firoozabadi
Ali Dehghani Firoozabadi
Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Published Date
- Jun 10, 2020
Expression levels of circulatory mir-185-5p, vascular endothelial growth factor, and platelet-derived growth factor target genes in endometriosis
Abstract
Background: Using blood-based biomarkers such as microRNAs (miRNAs) may allow particularly effective and minimally invasive diagnosis and treatment of endometriosis.
Objective: We evaluated the differential expression of circulating miRNA-185-5p (miR- 185-5p), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) target genes between endometriosis and healthy women.
Materials and Methods: 25 women with a history of endometriosis (grad III-IV) diagnosed by laparoscopy as the case group and 25 women without endometriosis underwent laparoscopy for ovarian cysts or pelvic pain as the control group were enrolled in this case-control study. Blood samples were obtained, and total RNA was used for high-throughput small RNA sequencing, and this was confirmed by means of quantitative real-time polymerase chain reaction (qRT-PCR).
Results: miRNA expression profiling using non-coding RNA sequencing revealed that one miRNA including miR-185-5p was significantly down-regulated in the case group compared with the controls. The qRT-PCR results showed significant downregulation of the expression level of miR-185-5p (p < 0.01) in the plasma of the case group. Receiver operating characteristic (ROC) curve analysis showed the area of miR-185-5p under the ROC curve for endometriosis diagnosis was 0.919 (p < 0.001). The RT-PCR results demonstrated that there was no significant difference in the expression of VEGF and PDGF mRNA of blood samples in the cases compared to the control group (PDGF, p = 0.09 and VEGF, p = 0.36).
Conclusion: The low expression of miR-185-5p in the plasma of women with endometriosis could be employed as an important non-invasive biomarker for early detection and screening of endometriosis by blood samples.
Key words: Biomarker, miRNA, Diagnosis, Endometriosis, Angiogenesis.
References
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[13] Yoshiji H, Harris SR, Thorgeirsson UP. Vascular endothelial growth factor is essential for initial but not continued in Vivo growth of human breast carcinoma cells. Cancer Res 1997; 57: 3924–3928.
[14] Guzick DS, Silliman NP, Adamson GD, Buttram VC Jr, Canis M, Malinak LR, et al. Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine’s revised classification of endometriosis. Fertil Steril 1997; 67: 822–829.
[15] Pösel C, Möller K, Fröhlich W, Schulz I, Boltze J, Wagner DC. Density gradient centrifugation compromises bone marrow mononuclear cell yield. PloS One 2012; 7: e50293.
[16] Ling G, Waxman DJ. DNase I digestion of isolated nulcei for genome-wide mapping of DNase hypersensitivity sites in chromatin. Methods Mol Biol 2013; 977: 21–33.
[17] McAlexander MA, Phillips MJ, Witwer KW. Comparison of methods for mirna extraction from plasma and quantitative recovery of RNA from cerebrospinal fluid. Front Genet 2013; 4: 83–90.
[18] Alamro RA, Mustafa M, Al-Asmari AK. Inflammatory gene mRna expression in human peripheral blood and its association with colorectal cancer. J Inflamm Res 2018; 11: 351–357.
[19] Agrawal S, Tapmeier T, Rahmioglu N, Kirtley S, Zondervan K, Becker C. The miRNA mirage: how close are we to finding a non-invasive diagnostic biomarker in endometriosis? A systematic review. Int J Mol Sci 2018; 19: e599–e624.
[20] Laschke MW, Menger MD. Basic mechanisms of vascularization in endometriosis and their clinical implications. Hum Reprod Update 2018; 24: 207–224.
[21] Gagne D, Page M, Robitaille G, Hugo P, Gosselin D. Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis. Hum Reprod 2003; 18: 1674–1680.
[22] Liu XJ, Bai XG, Teng YL, Song L, Lu N, Yang RQ. miRNA- 15a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. Eur Rev Med Pharmacol Sci 2016; 20: 3319–3326.
[23] Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 1998; 70: 425–431.
[24] Acimovic M, Vidakovic S, Milic N, Jeremic K, Markovic M, Milosevic-Djeric A, et al. Survivin and vegf as novel biomarkers in diagnosis of endometriosis/survivin i vegf kao novi biomarkeri u dijagnostici endometrioze. J Med Biochem 2016; 35: 63–68.
[25] Baranov VS, Ivaschenko TE, Liehr T, Yarmolinskaya MI. Systems genetics view of endometriosis: a common complex disorder. Eur J Obstet Gynecol Reprod Biol 2015; 185: 59–65.
[26] Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE, Dionyssopoulou E, et al. Serum concentrations of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines. Int Immunopharmacol 2003; 3: 81–89.
[27] McLaren J, Prentice A, Charnock-Jones DS, Smith SK. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod 1996; 11: 220–223.
[28] Pupo−Nogueira A, de Oliveira RM, Petta CA, Podgaec S, Dias Jr Jr, Abrao MS. Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis. Int J Gynecol Obstet 2007; 99: 33–37.
[29] Malhotra N, Karmakar D, Tripathi V, Luthra K, Kumar S. Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and presentation of endometriosis. Gynecol Endocrinol 2012; 28: 224–227.
[30] Lange S, Heger J, Euler G, Wartenberg M, Piper HM, Sauer H. Platelet-derived growth factor BB stimulates vasculogenesis of embryonic stem cell-derived endothelial cells by calcium-mediated generation of reactive oxygen species. Cardiovasc Res 2009; 81: 159–168.
[31] Cao R, Brakenhielm E, Li X, Pietras K, Widenfalk J, Ostman A, et al. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFRalphaalpha and -alphabeta receptors. FASEB J 2002; 16: 1575–1583.
[32] Magnusson PU, Looman C, Ahgren A, Wu Y, Claesson- Welsh L, Heuchel RL. Platelet-derived growth factor receptor-beta constitutive activity promotes angiogenesis in vivo and in vitro. Arterioscler Thromb Vasc Biol 2007; 27: 2142–2149.
[33] Laschke MW, Elitzsch A, Vollmar B, Vajkoczy P, Menger MD. Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions. Hum Reprod 2005; 21: 262–268.
[2] Zetter BR. Angiogenesis and tumor metastasis. Annual Review of Medicine 1998; 49: 407–424.
[3] Folkman J. Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002: 29 (suupl.); 15–18.
[4] Ribatti D, Vacca A, Presta M. The discovery of angiogenic factors: A historical review. Gen Pharmacol 2000; 35: 227–231.
[5] Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 2003; 9: 677–684.
[6] Ucuzian AA, Gassman AA, East AT, Greisler HP. Molecular mediators of angiogenesis. J Burn Care Res 2010; 31: 158–175.
[7] Mustonen T, Alitalo K. Endothelial receptor tyrosine kinases involved in angiogenesis. J Cell Biol 1995; 129: 895–898.
[8] Sato TN, Tozawa Y, Deutsch U, Wolburg-Buchholz K, Fujiwara Y, Gendron-Maguire M, et al. Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 1995; 376: 70–74.
[9] Raica M, Cimpean AM. Platelet-derived growth factor (PDGF)/PDGF receptors (PDGFR) axis as target for antitumor and antiangiogenic therapy. Pharmaceuticals 2010; 3: 572–599.
[10] Lindblom P, Gerhardt H, Liebner S, Abramsson A, Enge M, Hellstrom M, et al. Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 2003; 17: 1835–1840.
[11] Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res 2005; 97: 512–523.
[12] Presta M, Foglio E, Churruca Schuind A, Ronca R. Long Pentraxin-3 modulates the angiogenic activity of fibroblast growth factor-2. Front Immunol 2018; 9: 2327–2335.
[13] Yoshiji H, Harris SR, Thorgeirsson UP. Vascular endothelial growth factor is essential for initial but not continued in Vivo growth of human breast carcinoma cells. Cancer Res 1997; 57: 3924–3928.
[14] Guzick DS, Silliman NP, Adamson GD, Buttram VC Jr, Canis M, Malinak LR, et al. Prediction of pregnancy in infertile women based on the American Society for Reproductive Medicine’s revised classification of endometriosis. Fertil Steril 1997; 67: 822–829.
[15] Pösel C, Möller K, Fröhlich W, Schulz I, Boltze J, Wagner DC. Density gradient centrifugation compromises bone marrow mononuclear cell yield. PloS One 2012; 7: e50293.
[16] Ling G, Waxman DJ. DNase I digestion of isolated nulcei for genome-wide mapping of DNase hypersensitivity sites in chromatin. Methods Mol Biol 2013; 977: 21–33.
[17] McAlexander MA, Phillips MJ, Witwer KW. Comparison of methods for mirna extraction from plasma and quantitative recovery of RNA from cerebrospinal fluid. Front Genet 2013; 4: 83–90.
[18] Alamro RA, Mustafa M, Al-Asmari AK. Inflammatory gene mRna expression in human peripheral blood and its association with colorectal cancer. J Inflamm Res 2018; 11: 351–357.
[19] Agrawal S, Tapmeier T, Rahmioglu N, Kirtley S, Zondervan K, Becker C. The miRNA mirage: how close are we to finding a non-invasive diagnostic biomarker in endometriosis? A systematic review. Int J Mol Sci 2018; 19: e599–e624.
[20] Laschke MW, Menger MD. Basic mechanisms of vascularization in endometriosis and their clinical implications. Hum Reprod Update 2018; 24: 207–224.
[21] Gagne D, Page M, Robitaille G, Hugo P, Gosselin D. Levels of vascular endothelial growth factor (VEGF) in serum of patients with endometriosis. Hum Reprod 2003; 18: 1674–1680.
[22] Liu XJ, Bai XG, Teng YL, Song L, Lu N, Yang RQ. miRNA- 15a-5p regulates VEGFA in endometrial mesenchymal stem cells and contributes to the pathogenesis of endometriosis. Eur Rev Med Pharmacol Sci 2016; 20: 3319–3326.
[23] Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 1998; 70: 425–431.
[24] Acimovic M, Vidakovic S, Milic N, Jeremic K, Markovic M, Milosevic-Djeric A, et al. Survivin and vegf as novel biomarkers in diagnosis of endometriosis/survivin i vegf kao novi biomarkeri u dijagnostici endometrioze. J Med Biochem 2016; 35: 63–68.
[25] Baranov VS, Ivaschenko TE, Liehr T, Yarmolinskaya MI. Systems genetics view of endometriosis: a common complex disorder. Eur J Obstet Gynecol Reprod Biol 2015; 185: 59–65.
[26] Matalliotakis IM, Goumenou AG, Koumantakis GE, Neonaki MA, Koumantakis EE, Dionyssopoulou E, et al. Serum concentrations of growth factors in women with and without endometriosis: the action of anti-endometriosis medicines. Int Immunopharmacol 2003; 3: 81–89.
[27] McLaren J, Prentice A, Charnock-Jones DS, Smith SK. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod 1996; 11: 220–223.
[28] Pupo−Nogueira A, de Oliveira RM, Petta CA, Podgaec S, Dias Jr Jr, Abrao MS. Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis. Int J Gynecol Obstet 2007; 99: 33–37.
[29] Malhotra N, Karmakar D, Tripathi V, Luthra K, Kumar S. Correlation of angiogenic cytokines-leptin and IL-8 in stage, type and presentation of endometriosis. Gynecol Endocrinol 2012; 28: 224–227.
[30] Lange S, Heger J, Euler G, Wartenberg M, Piper HM, Sauer H. Platelet-derived growth factor BB stimulates vasculogenesis of embryonic stem cell-derived endothelial cells by calcium-mediated generation of reactive oxygen species. Cardiovasc Res 2009; 81: 159–168.
[31] Cao R, Brakenhielm E, Li X, Pietras K, Widenfalk J, Ostman A, et al. Angiogenesis stimulated by PDGF-CC, a novel member in the PDGF family, involves activation of PDGFRalphaalpha and -alphabeta receptors. FASEB J 2002; 16: 1575–1583.
[32] Magnusson PU, Looman C, Ahgren A, Wu Y, Claesson- Welsh L, Heuchel RL. Platelet-derived growth factor receptor-beta constitutive activity promotes angiogenesis in vivo and in vitro. Arterioscler Thromb Vasc Biol 2007; 27: 2142–2149.
[33] Laschke MW, Elitzsch A, Vollmar B, Vajkoczy P, Menger MD. Combined inhibition of vascular endothelial growth factor (VEGF), fibroblast growth factor and platelet-derived growth factor, but not inhibition of VEGF alone, effectively suppresses angiogenesis and vessel maturation in endometriotic lesions. Hum Reprod 2005; 21: 262–268.