Skip to main content

Advertisement

SpringerLink
Log in

Silencing of SRA1 Regulates ER Expression and Attenuates the Growth of Stromal Cells in Ovarian Endometriosis

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

Abstract

Estradiol and its nuclear receptors, estrogen receptor (ER) α and ER-β, have important functions in endometriosis, and the transcriptional activity of these receptors is modulated by coactivators and corepressors. The steroid receptor RNA activator 1 (SRA1) produces SRA long noncoding RNA (lncRNA) and SRA protein (SRAP), which regulate ER expression at the RNA and protein levels in some hormone-dependent tumors via an alternative splicing event. However, only a few are reported on their expressions in endometriosis. Here, we observed that low expression levels of SRA lncRNA and ER-α but relatively high expression levels of SRAP and ER-β were detected in ovarian endometriotic tissues versus normal endometrial tissues. Steroid receptor RNA activator I-small interfering RNA treatment significantly increased ER-α levels but reduced ER-β levels in endometriotic stromal cells (ESCs). Furthermore, the treatment can also attenuate the proliferation and promote early apoptosis in these cells. Our results indicate that the regulation of ER via SRA in ovarian endometriosis may play a significant role in the growth of ESCs.

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. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–1799.

    Google Scholar 

  2. Trukhacheva E, Lin Z, Reierstad S, Cheng Y, Milad M, Bulun SE. Estrogen receptor (ER)-β regulates ER-α expression in stromal cells derived from ovarian endometriosis. J Clin Endocrinol Metab. 2009;94(2):615–622.

    Article  CAS  Google Scholar 

  3. Lanz RB, McKenna NJ, Onate SA, et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell. 1999;97(1):17–27.

    Article  CAS  Google Scholar 

  4. Hube F, Guo J, Chooniedass-Kothari S, et al. Alternative splicing of the first intron of the steroid receptor RNA activator (SRA) participates in the generation of coding and noncoding RNA iso-forms in breast cancer cell lines. DNA Cell Biol. 2006;25(7):418–428.

    Article  CAS  Google Scholar 

  5. McKay DB, Xi L, Barthel KK, Cech TR. Structure and function of steroid receptor RNA activator protein, the proposed partner of SRA noncoding RNA. J Mol Biol. 2014;426(8):1766–1785.

    Article  CAS  Google Scholar 

  6. Coleman KM, Lam V, Jaber BM, Lanz RB, Smith CL. SRA coactivation of estrogen receptor-alpha is phosphorylation-independent, and enhances 4-hydroxytamoxifen agonist activity. Biochem Biophys Res Commun. 2004;323(1):332–338.

    Article  CAS  Google Scholar 

  7. Cooper C, Guo J, Yan Y, et al. Increasing the relative expression of endogenous non-coding Steroid Receptor RNA Activator (SRA) in human breast cancer cells using modified oligonucleo-tides. Nucleic Acids Res. 2009;37(13):4518–4531.

    Article  CAS  Google Scholar 

  8. Deblois G, Giguere V. Ligand-independent coactivation of ERal-pha AF-1 by steroid receptor RNA activator (SRA) via MAPK activation. J Steroid BiochemMol Biol. 2003;85(2-5):123–131.

    Article  CAS  Google Scholar 

  9. Klinge CM, Jernigan SC, Mattingly KA, Risinger KE, Zhang J. Estrogen response element-dependent regulation of tran-scriptional activation of estrogen receptors alpha and beta by coactivators and corepressors. J Mol Endocrinol. 2004;33(2):387–410.

    Article  CAS  Google Scholar 

  10. Watanabe M, Yanagisawa J, Kitagawa H, et al. A subfamily of RNA-binding DEAD-box proteins acts as an estrogen receptor coactivator through the N-terminal activation domain (AF-1) with an RNA coactivator, SRA. EMBOJ. 2001;20(6):1341–1352.

    Article  CAS  Google Scholar 

  11. Chooniedass-Kothari S, Vincett D, Yan Y, et al. The protein encoded by the functional steroid receptor RNA activator is a new modulator of ER alpha transcriptional activity. FEBS Lett. 2010;584(6):1174–1180.

    Article  CAS  Google Scholar 

  12. Lin K, Ma J, Wu R, Zhou C, Lin J. Influence of ovarian endome-trioma on expression of steroid receptor RNA activator, estrogen receptors, vascular endothelial growth factor, and thrombospon-din 1 in the surrounding ovarian tissues. Reprod Sci. 2014;21(2):183–189.

    Article  Google Scholar 

  13. Lin K, Zhan H, Ma J, et al. Increased steroid receptor RNA activator protein (SRAP) accompanied by decreased estrogen receptor-beta (ER-b) levels during the malignant transformation of endometriosis associated ovarian clear cell carcinoma. Acta Histochem. 2014;116(5):878–882.

    Article  CAS  Google Scholar 

  14. Jiang QY, Xia JM, Ding HG, Fei XW, Lin J, Wu RJ. RNAi-mediated blocking of ezrin reduces migration of ectopic endome-trial cells in endometriosis. Mol Hum Reprod. 2012;18(9):435–441.

    Article  CAS  Google Scholar 

  15. Friel AM, Sexton DJ, O’reilly MW, Smith TJ, Morrison JJ. Rho A/Rho kinase: human umbilical artery mRNA expression in normal and preeclamptic pregnancies and functional role in isoprostane-induced vasoconstriction. Reproduction. 2006;132(1):169–176.

    Article  CAS  Google Scholar 

  16. Zhu R, Xu R, Jiang X, et al. Expression profile of cancer-related genes in human adult bone marrow-derived neural stem like cells highlights the need for tumorigenicity study. J Neurosci Res. 2007;85(14):3064–3070.

    Article  CAS  Google Scholar 

  17. Pang J, Liu WP, Liu XP, et al. Profiling protein markers associated with lymph node metastasis in prostate cancer by DIGE-based proteomics analysis. J Proteome Res. 2010;9(1):216–226.

    Article  CAS  Google Scholar 

  18. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T)) method. Methods. 2001;25(4):402–408.

    Article  CAS  Google Scholar 

  19. Chooniedass-Kothari S, Emberley E, Hamedani MK, et al. The steroid receptor RNA activator is the first functional RNA encoding a protein. FEBS Lett. 2004;566(1-3):43–47.

    Article  CAS  Google Scholar 

  20. Emberley E, Huang GJ, Hamedani MK, et al. Identification of new human coding steroid receptor RNA activator isoforms. Biochem Biophys Res Commun. 2003;301(2):509–515.

    Article  CAS  Google Scholar 

  21. Li X, Darzynkiewicz Z. Labelling DNA strand breaks with BrdUTP. Detection of apoptosis and cell proliferation. Cell Prolif. 1995;28(11):571–579.

    CAS  PubMed  Google Scholar 

  22. Black DL. Mechanisms of alternative pre-messenger RNA splicing. Annu Rev Biochem. 2003;72:291-336.

    Article  CAS  Google Scholar 

  23. Black DL, Grabowski PJ. Alternative pre-mRNA splicing and neuronal function. Progr Mol Subcell Biol. 2003;31:187-216.

    Article  CAS  Google Scholar 

  24. Lee CJ, Irizarry K. Alternative splicing in the nervous system: an emerging source of diversity and regulation. Biol Psychiatry. 2003;54(8):771–776.

    Article  CAS  Google Scholar 

  25. Xue Q, Lin Z, Cheng YH, et al. Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod. 2007;77(4):681–687.

    Article  CAS  Google Scholar 

  26. Fazleabas AT, Brudney A, Chai D, Langoi D, Bulun SE. Steroid receptor and aromatase expression in baboon endometriotic lesions. Fertil Steril. 2003;80(suppl 2):820–827.

    Article  Google Scholar 

  27. Hube F, Velasco G, Rollin J, Furling D, Francastel C. Steroid receptor RNA activator protein binds to and counteracts SRA RNA-mediated activation of MyoD and muscle differentiation. Nucleic Acids Res. 2011;39(2):513–525.

    Article  CAS  Google Scholar 

  28. Cooper C, Vincett D, Yan Y, Hamedani MK, Myal Y, Leygue E. Steroid receptor RNA activator bi-faceted genetic system: heads or tails? Biochimie. 2011;93(11):1973–1980.

    Article  CAS  Google Scholar 

  29. Lanz RB, Razani B, Goldberg AD, O’Malley BW. Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA). Proc Natl Acad Sci USA. 2002;99(25):16081–16086.

    Article  CAS  Google Scholar 

  30. Zhao X, Patton JR, Davis SL, Florence B, Ames SJ, Spanjaard RA. Regulation of nuclear receptor activity by a pseudouridine synthase through posttranscriptional modification of steroid receptor RNA activator. Mol Cell. 2004;15(4):549–558.

    Article  CAS  Google Scholar 

  31. Borth N, Massier J, Franke C, Sachse K, Saluz HP, Hanel F. Chlamydial protease CT441 interacts with SRAP1 co-activator of estrogen receptor alpha and partially alleviates its co-activation activity. J Steroid Biochem Mol Biol. 2010;119(1-2): 89–95.

    Article  CAS  Google Scholar 

  32. Kawashima H, Takano H, Sugita S, Takahara Y, Sugimura K, Nakatani T. A novel steroid receptor co-activator protein (SRAP) as an alternative form of steroid receptor RNA-activator gene: expression in prostate cancer cells and enhancement of androgen receptor activity. Biochem J. 2003;369(pt 1):163–171.

    Article  CAS  Google Scholar 

  33. Kurisu T, Tanaka T, Ishii J, et al. Expression and function of human steroid receptor RNA activator in prostate cancer cells: role of endogenous hSRA protein in androgen receptor-mediated transcription. Prostate Cancer Prostatic Dis. 2006;9(2):173–178.

    Article  CAS  Google Scholar 

  34. Chooniedass-Kothari S, Hamedani MK, Auge C, et al. The steroid receptor RNA activator protein is recruited to promoter regions and acts as a transcriptional repressor. FEBS Lett. 2010;584(11):2218–2224.

    Article  CAS  Google Scholar 

  35. Bulun SE. Endometriosis. N Engl J Med. 2009;360(3):268–279.

    Article  CAS  Google Scholar 

  36. Di Ruscio A, Ebralidze AK, Benoukraf T, et al. DNMT1-interacting RNAs block gene-specific DNA methylation. Nature. 2013;503(7476):371–376.

    Article  Google Scholar 

  37. Arab K, Park YJ, Lindroth AM, et al. Long noncoding RNA TARID directs demethylation and activation of the tumor suppressor TCF21 via GADD45A. Mol Cell. 2014;55(4):604–614.

    Article  CAS  Google Scholar 

  38. Leygue E. Steroid receptor RNA activator (SRA1): unusual bifa-ceted gene products with suspected relevance to breast cancer. Nucl Recept Signal. 2007;5:e006.

    Article  Google Scholar 

  39. Foulds CE, Tsimelzon A, Long W, et al. Research resource: expression profiling reveals unexpected targets and functions of the human steroid receptor RNA activator (SRA) gene. Mol Endocrinol. 2010;24(5):1090–1105.

    Article  CAS  Google Scholar 

  40. Yan Y, Skliris GP, Penner C, et al. Steroid Receptor RNA Activator Protein (SRAP): a potential new prognostic marker for estrogen receptor-positive/node-negative/younger breast cancer patients. Breast Cancer Res. 2009;11(5):R67.

    Article  Google Scholar 

  41. Han SJ, Jung SY, Wu SP, et al. Estrogen receptor beta modulates apoptosis complexes and the inflammasome to drive the patho-genesis of endometriosis. Cell. 2015;163(4):960–974.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Gynaecology, Women’s Hospital, Zhejiang University School of Medicine, 1 Xueshi Road, Hangzhou, Zhejiang, 310006, People’s Republic of China

    Kaiqing Lin MD, Hong Zhan MD, Kaihong Xu MD, Ruijin Wu MD & Jun Lin MD

  2. Key Laboratory of Women’s Reproductive Health of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China

    Junyan Ma MD

  3. Department of Pathology, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China

    Caiyun Zhou MD

Authors
  1. Kaiqing Lin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Zhan MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junyan Ma MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kaihong Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ruijin Wu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Caiyun Zhou MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jun Lin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jun Lin MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, K., Zhan, H., Ma, J. et al. Silencing of SRA1 Regulates ER Expression and Attenuates the Growth of Stromal Cells in Ovarian Endometriosis. Reprod. Sci. 24, 836–843 (2017). https://doi.org/10.1177/1933719116670036

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719116670036

Keywords

Search

Navigation