Skip to main content

Advertisement

SpringerLink
Log in

Circulating miRNAs in Murine Experimental Endometriosis: Decreased Abundance of let-7a

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

Abstract

Endometriosis is a chronic disease that commonly affects women of reproductive age; however, diagnosis is often delayed due to lack of appreciation of early signs and symptoms. Development of a noninvasive biomarker would significantly reduce delays in diagnosis and treatment. Circulating microRNAs (miRNAs) have been implicated as biomarkers for several diseases including endometriosis. Here, we use an miRNA array to investigate differential miRNA abundance in the serum of mice after induction of experimental endometriosis. let-7a-5p was decreased in the serum of mice with endometriosis. let-7b-5p, c-5p, and e-5p also showed a trend toward downregulation. Serum let-7 family miRNA shows similar dysregulation in endometriosis in both humans and mice. Diminished circulating let-7 implies a complex regulation that potentially involves multiple organs. Further investigation is necessary to determine the functional roles of let-7 miRNAs in this disease.

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. Cho S, Mutlu L, Grechukhina O, Taylor HS. Circulating microRNAs as potential biomarkers for endometriosis. Fertil Steril. 2015;103(5):1252–1260.e1. doi:10.1016/j.fertnstert.2015.02.013.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Macer ML, Taylor HS. Endometriosis and Infertility. A review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535–549. doi:10.1016/j.ogc.2012.10.002.

    PubMed  PubMed Central  Google Scholar 

  3. Dunselman GA, Vermeulen N, Becker C, et al.; European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod. 2014;29(3):400–412. doi:10.1093/humrep/det457.

    CAS  PubMed  Google Scholar 

  4. Husby GK, Haugen RS, Moen MH. Diagnostic delay in women with pain and endometriosis. Acta Obstet Gynecol Scand. 2003;82(7):649–653. doi:10.1034/j.1600-0412.2003.00168.x.

    PubMed  Google Scholar 

  5. Vodolazkaia A, El-Aalamat Y, Popovic D, et al. Evaluation of a panel of 28 biomarkers for the non-invasive diagnosis of endometriosis. Hum Reprod. 2012;27(9):2698–2711. doi:10.1093/humrep/des234.

    CAS  PubMed  Google Scholar 

  6. Ohlsson Teague EMC, Print CG, Hull ML. The role of microRNAs in endometriosis and associated reproductive conditions. Hum Reprod Update. 2009;16(2):142–165. doi:10.1093/humupd/dmp034.

    Google Scholar 

  7. Vicente-Muñoz S, Morcillo I, Puchades-Carrasco L, Payá V, Pellicer A, Pineda-Lucena A. Nuclear magnetic resonance metabolomic profiling of urine provides a noninvasive alternative to the identification of biomarkers associated with endometriosis. Fertil Steril. 2015;104(5):1202–1209. doi: https://doi.org/10.1016/j.fertnstert.2015.07.1149.

    PubMed  Google Scholar 

  8. Ferrero S, Gillott DJ, Remorgida V, Anserini P, Ragni N, Grudzinskas JG. Peritoneal fluid proteome in women with different ASRM stages of endometriosis. Gynecol Endocrinol. 2008;24(8):433–441. doi:10.1080/09513590802173824.

    CAS  PubMed  Google Scholar 

  9. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):228–234. doi:10.1038/ncb0309-228.

    CAS  PubMed  Google Scholar 

  10. Lawrie CH, Gal S, Dunlop M, et al. Detection of elevated levels of tumour-associated microRNAs in serum of patients with diffuse large B-cell lymphoma. Br J Haematol. 2008;141(5):672–675. doi:10.1111/j.1365-2141.2008.07077.x.

    PubMed  Google Scholar 

  11. Cortez MA, Bueso-Ramos C, Ferdin J, Lopez-Berestein G, Sood AK, Calin GA. MicroRNAs in body fluids - the mix of hormones and biomarkers. Nat Rev Clin Oncol. 2011;8(8):467–477. doi:10.1038/nrclinonc.2011.76.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Creemers EE, Tijsen AJ, Pinto YM. Circulating MicroRNAs: novel biomarkers and extracellular communicators in cardiovascular disease?.Circ Res. 2012;110(3):483–495. doi:10.1161/CIRCRESAHA.111.247452.

    CAS  PubMed  Google Scholar 

  13. Nakasa T, Miyaki S, Okubo A, et al. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis Rheum. 2008;58(5):1284–1292. doi:10.1002/art.23429.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang J, Yu M, Yu G, et al. Serum miR-146a and miR-223 as potential new biomarkers for sepsis. Biochem Biophys Res Commun. 2010;394(1):184–188. doi:10.1016/j.bbrc.2010.02.145.

    CAS  PubMed  Google Scholar 

  15. Jia SZ, Yang Y, Lang J, Sun P, Leng J. Plasma miR-17-5p, miR-20a and miR-22 are down-regulated in women with endometriosis. Hum Reprod. 2013;28(2):322–330. doi:10.1093/humrep/des413.

    CAS  PubMed  Google Scholar 

  16. Suryawanshi S, Vlad AM, Lin H, et al. Plasma MicroRNAs as novel biomarkers for endometriosis and endometriosis-associated ovarian cancer. Clin Cancer Res. 2013;(2):1213–1225. doi:10.1158/1078-0432.CCR-12-2726.

    Google Scholar 

  17. Rekker K, Sc M, Saare M, et al. Circulating miR-200 - family micro-RNAs have altered plasma levels in patients with endometriosis and vary with blood collection time. Fertil Steril. 2015;104(1):938–946. doi:10.1016/j.fertnstert.2015.06.029.

    Google Scholar 

  18. Cosar E, Mamillapalli R, Ersoy GS, Cho S, Seifer B, Taylor HS. Serum microRNAs as diagnostic markers of endometriosis: a comprehensive array-based analysis. Fertil Steril. 2016;(1):1–8. doi:10.1016/j.fertnstert.2016.04.013.

    Google Scholar 

  19. Kirschner MB, Edelman JJB, Kao SC, Michael P, Reid G. The impact of hemolysis on cell-free microRNA biomarkers. Front Genet. 2013;4:94:1–13. doi:10.3389/fgene.2013.00094.

    Google Scholar 

  20. Blondal T, Jensby Nielsen S, Baker A, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods. 2013;59(1):S1–S6. doi:10.1016/j.ymeth.2012.09.015.

    CAS  PubMed  Google Scholar 

  21. Busk PK. A tool for design of primers for microRNA-specific quantitative RT-qPCR. BMC Bioinformatics. 2014;15(1):29. doi:10.1186/1471-2105-15-29.

    PubMed  PubMed Central  Google Scholar 

  22. Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol. 2008;18(10):505–516. doi:10.1016/j.tcb.2008.07.007.

    CAS  PubMed  Google Scholar 

  23. Grechukhina O, Petracco R, Popkhadze S, et al. A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis. EMBO Mol Med. 2012;4(3):206–217. doi:10.1002/emmm.201100200.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Ghazal S, McKinnon B, Zhou J, et al. H19 lncRNA alters stromal cell growth via IGF signaling in the endometrium of women with endometriosis. EMBO Mol Med. 2015;7(8):1–8. doi:10.15252/emmm.201505245.

    Google Scholar 

  25. Yan L, Zhou J, Gao Y, et al. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene. 2015;34(23):3076–3084. doi:10.1038/onc.2014.236.

    CAS  PubMed  Google Scholar 

  26. Hameiri-Grossman M, Porat-Klein A, Yaniv I, et al. The association between let-7, RAS and HIF-1α in Ewing Sarcoma tumor growth. Oncotarget. 2015;6(32):33834–33848. doi:10.18632/oncotarget.5616.

    PubMed  PubMed Central  Google Scholar 

  27. Hikasa H, Sekido Y, Suzuki A. Merlin/NF2-Lin28B-let-7 is a tumor-suppressive pathway that is cell-density dependent and hippo independent. Cell Rep. 2016;14(12):2950–2961. doi:10.1016/j.celrep.2016.02.075.

    CAS  PubMed  Google Scholar 

  28. Zhang Z, Huang L, Yu Z, et al. Let-7a functions as a tumor suppressor in Ewing’s sarcoma cell lines partly by targeting cyclin-dependent kinase 6. DNA Cell Biol. 2014;33(3):136–147. doi:10.1089/dna.2013.2179.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu K, Zhang C, Li T, Ding Y, Tu T. Let-7a inhibits growth and migration of breast cancer cells by targeting HMGA1. Int J Oncol. 2015;46(6):2526–2534. doi:10.3892/ijo.2015.2949.

    CAS  PubMed  Google Scholar 

  30. Zhang Z, Li Y, Huang L, et al. Let-7a suppresses macrophage infiltrations and malignant phenotype of Ewing sarcoma via STAT3/NF-κB positive regulatory circuit. Cancer Lett. 2016;374(2):192–201. doi:10.1016/j.canlet.2016.02.027.

    CAS  PubMed  Google Scholar 

  31. Liu Y, Yin B, Zhang C, Zhou L, Fan J. Hsa-let-7a functions as a tumor suppressor in renal cell carcinoma cell lines by targeting c-myc. Biochem Biophys Res Commun. 2012;417(1):371–375. doi:10.1016/j.bbrc.2011.11.119.

    CAS  PubMed  Google Scholar 

  32. Jung YJ, Isaacs JS, Lee S, Trepel J, Neckers L. IL-1beta-mediated up-regulation of HIF-1alpha via an NFkappaB/COX-2 pathway identifies HIF-1 as a critical link between inflammation and oncogenesis. FASEB J. 2003;17(14):2115–2117. doi:10.1096/fj.03-0329fje.

    CAS  PubMed  Google Scholar 

  33. Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998;13(6):1686–1690.

    CAS  PubMed  Google Scholar 

  34. Schwarzenbach H, Nishida N, Calin GA, Pantel K. Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 2014;11(3):145–156. doi:10.1038/nrclinonc.2014.5.

    CAS  PubMed  Google Scholar 

  35. Sung SY, Liao CH, Wu HP, et al. Loss of let-7 microRNA upregulates IL-6 in bone marrow-derived mesenchymal stem cells triggering a reactive stromal response to prostate cancer. PLoS One. 2013;8(8):e71637. doi:10.1371/journal.pone.0071637.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Beachy SH, Onozawa M, Chung YJ, et al. Enforced expression of Lin28b leads to impaired T-cell development, release of inflammatory cytokines, and peripheral T-cell lymphoma. Blood. 2012;120(5):1048–1059. doi:10.1182/blood-2012-01-401760.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 2009;139(4):693–706. doi:10.1016/j.cell.2009.10.014.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Gong Z, Zhao S, Zhang J, et al. Initial research on the relationship between let-7 family members in the serum and massive cerebral infarction. J Neurol Sci. 2016;361:150–157. doi:10.1016/j.jns.2015.12.047.

    CAS  PubMed  Google Scholar 

  39. Monsanto SP, Edwards AK, Zhou J, et al. Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients. Fertil Steril. 2016;105(4):968–977.e5. doi:10.1016/j.fertnstert.2015.11.047.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics, Yale School of Medicine, Gynecology, and Reproductive Sciences, 333 Cedar Street, New Haven, CT, 06520, USA

    Benjamin J. Seifer BS, Dan Su PhD & Hugh S. Taylor MD

Authors
  1. Benjamin J. Seifer BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dan Su PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hugh S. Taylor MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hugh S. Taylor MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Seifer, B.J., Su, D. & Taylor, H.S. Circulating miRNAs in Murine Experimental Endometriosis: Decreased Abundance of let-7a. Reprod. Sci. 24, 376–381 (2017). https://doi.org/10.1177/1933719116667228

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719116667228

Keywords

Search

Navigation