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Integrated Data Set of microRNAs and mRNAs Involved in Severe Intrauterine Adhesion

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Abstract

Background

Adhesion tissue is formed following injury to the uterine basal layer. Currently, there is no effective treatment for severe intrauterine adhesion (IUA),which causes loss of reproductive function. Enhanced understanding of themolecular mechanisms driving severe IUAwould be beneficial for the treatment.

Methods

Differentially expressed microRNAs (miRNAs) and messenger RNAs (mRNAs) in severe IUA (n = 3) and normal (n = 3) endometrium were analyzed by high-throughput microarray analysis. Subsequently, the target genes of the differentially expressed miRNAs were predicted and found to overlap with the differentially expressed mRNAs. Gene Ontology and pathway analyses were performed for the intersecting genes. Three of the significantly dysregulated miRNAs and 4 of their target mRNAs were further assessed using quantitative real-time polymerase chain reaction (PCR) in 10 severe IUA and 10 normal endometrium samples.

Results

Microarray analysis indicated that 26 miRNAs and 1180 mRNAs were significantly different between the 2 groups. Of these, 16 miRNAs and 54 mRNAs overlapped with putative miRNA target genes and prediction of target gene. Real-time PCR revealed upregulation of hsa-miR-513a-5p and has-miR-135a-3p and downregulation of hsa-miR-543 and their corresponding target genes, plus downregulation of ADAM9 (a disintegrin-containing and metalloproteinases) and lysyl oxidase and upregulation of CDH2 (N-cadherin) and COLI6AI (collagen 16A1). Both CDH2 and COLI6AI were bioinformatically predicted and confirmed in vitro as target genes of miR-543.

Conclusion

This study provides an integrated data set of the miRNA and mRNA profiles in severe IUA, showing involvement of many miRNAs and their target genes. Further analysis of these genes will help in understanding of the molecular mechanism of IUA formation.

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References

  1. Tam, WH, Lau, WC, Cheung, LP, Yuen, PM, Chung, TK Intrau-terine adhesions after conservative and surgical management of spontaneous abortion. J Am Assoc Gynecol Laparosc. 2002;9(2): 182–185.

    Article  PubMed  Google Scholar 

  2. Yu, D, Li, TC, Xia, E, Huang, X, Liu, Y, Peng, X Factors affecting reproductive outcome of hysteroscopic adhesiolysis for Asher-man syndrome. Fertil Steril. 2008;89(3):715–722.

    Article  PubMed  Google Scholar 

  3. Bavan, L, Midwood, K, Nanchahal, J MicroRNA epigenetics: a new avenue for wound healing research. BioDrugs. 2011;25(1):27–41.

    Article  CAS  PubMed  Google Scholar 

  4. The American Fertility Society classifications of adnexal adhe-sions, distal tubal occlusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, mullerian anomalies and intrauterine adhesions. Fertil Steril. 1988;49(6):944–955.

    Article  Google Scholar 

  5. Clarke, R, Ressom, HW, Wang, A, et al. The properties of high-dimensional data spaces: implications for exploring gene and protein expression data. Nat Rev Cancer. 2008;8(1):37–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Schlitt, T, Palin, K, Rung, J, et al. From gene networks to gene function. Genome Res. 2003;13(12):2568–2576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Draghici, S, Khatri, P, Tarca, AL, et al. A systems biology approach for pathway level analysis. Genome Res. 2007;17(10):1537–1545.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Joung, JG, Hwang, KB, Nam, JW, Kim, SJ, Zhang, BT Discovery of microRNA-mRNA modules via population-based probabilistic learning. Bioinformatics. 2007;23(9):1141–1147.

    Article  CAS  PubMed  Google Scholar 

  9. March, CM Asherman’s syndrome. Semin Reprod Med. 2011; 29(2):83–94.

    Article  PubMed  Google Scholar 

  10. Buckley, CH Normal endometrium and non-proliferative condi-tions of the endometrium. In: Fox, H, Wells, M, eds. Obstetrical and Gynaecological Pathology. 5th ed. London, United Kindom: Churchill Livingstone; 2002:391.

    Google Scholar 

  11. Yaffe, H, Ron, M, Polishuk, WZ Amenorrhoea, hypomenor-rhoea and uterine fibrosis. Am J Obstet Gynecol. 1978; 130(5):599–601.

    Article  CAS  PubMed  Google Scholar 

  12. Chegini, N Peritoneal molecular environment, adhesion formation and clinical implication. Front Biosci. 2002;7:e91–e115.

    CAS  PubMed  Google Scholar 

  13. Midwood, KS, Williams, LV, Schwarzbauer, JE Tissue repair and the dynamics of the extracellular matrix. Int J Biochem Cell Biol. 2004;36(6):1031–1037.

    Article  CAS  PubMed  Google Scholar 

  14. Jiang, X, Tsitsiou, E, Herrick, SE, Lindsay, MA microRNAs and the regulation of fibrosis. FEBS, J 2010;277(9):2015–2021.

    Article  CAS  Google Scholar 

  15. Wu, H, Zhu, S, Mo, YY Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res. 2009;19(4):439–448.

    Article  CAS  PubMed  Google Scholar 

  16. Ferguson, MW, O’Kane, S Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci. 2004;359(1445):839–850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhao, Y, Srivastava, D A developmental view of micro-RNA function. Trends Biochem Sci. 2007;32(4):189–197.

    Article  CAS  PubMed  Google Scholar 

  18. Brasch, J, Harrison, OJ, Ahlsen, G, et al. Structure and binding mechanism of vascular endothelial cadherin: a divergent classical cadherin. J Mol Biol. 2011;408(1):57–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. D’Amour, KA, Agulnick, AD, Eliazer, S, Kelly, OG, Kroon, E, Baetge, EE Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol. 2005;23(12): 1534–1541.

    Article  PubMed  Google Scholar 

  20. Li, C, Nguyen, HT, Zhuang, Y, et al. Post-transcriptional up-regulation of miR-21 by type I collagen. Mol Carcinog. 2011; 50(7):563–570.

    Article  CAS  PubMed  Google Scholar 

  21. Cheng, J, Wang, Y, Wang, D, Wu, Y Identification of collagen 1 as a post-transcriptional target of miR-29b in skin fibroblasts: ther-apeutic implication for scar reduction. Am J Med Sci. 2013; 346(2):98–103.

    Article  PubMed  Google Scholar 

  22. Zitka, O, Kukacka, J, Krizkova, S, et al. Matrix metalloproteinases. Curr Med Chem. 2010;17(31):3751–3768.

    Article  CAS  PubMed  Google Scholar 

  23. Mauch, C, Zamek, J, Abety, AN, Grimberg, G, Fox, JW, Zigrino, P Accelerated wound repair in ADAM-9 knockout animals. J Invest Dermatol. 2010;130(8):2120–2130.

    Article  CAS  PubMed  Google Scholar 

  24. Tadmor, T, Bejar, J, Attias, D, et al. The expression of lysyl-oxidase gene family members in myeloproliferative neoplasms. Am J Hematol. 2013;88(5):355–358.

    Article  CAS  PubMed  Google Scholar 

  25. Perepelyuk, M, Terajima, M, Wang, AY, et al. Hepatic stellate cells and portal fibroblasts are the major cellular sources of collagens and lysyl oxidases in normal liver and early after injury. Am J Physiol Gastrointest Liver Physiol. 2013;304(6):g605–g614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liang, P, Lv, C, Jiang, B, et al. MicroRNA profiling in denatured dermis of deep burn patients. Burns. 2012;38(4):534–540.

    Article  PubMed  Google Scholar 

  27. Cheng, J, Yu, H, Deng, S, Shen, G MicroRNA profiling in mid- and late-gestational fetal skin: implication for scarless wound healing. Tohoku J Exp Med. 2010;221(3):203–209.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Minimally Invasive Gynecology, Obstetrics and Gynecology Hospital Beijing, Capital Medical University, Beijing, 100006, China

    Xin Liu PhD, Hua Duan PhD, Lu Gan MD & Qian Xu MD

  2. Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking University Hepatology Institute, Peking University People’s Hospital, Beijing, PR China

    Heng-Hui Zhang PhD

Authors
  1. Xin Liu PhD
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  2. Hua Duan PhD
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  3. Heng-Hui Zhang PhD
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  4. Lu Gan MD
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  5. Qian Xu MD
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Corresponding authors

Correspondence to Hua Duan PhD or Heng-Hui Zhang PhD.

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Liu, X., Duan, H., Zhang, HH. et al. Integrated Data Set of microRNAs and mRNAs Involved in Severe Intrauterine Adhesion. Reprod. Sci. 23, 1340–1347 (2016). https://doi.org/10.1177/1933719116638177

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  • DOI: https://doi.org/10.1177/1933719116638177

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