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The clinical significance of circulating DSCAM-AS1 in patients with ER-positive breast cancer and construction of its competitive endogenous RNA network

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Abstract

Long Non-Coding RNAs (lncRNAs), with diagnostic and therapeutic applications in malignancies, are newly described tumour-related molecules. Here, we reported the importance of circulating DSCAM-AS1 as the biomarker to detect Estrogen Receptor (ER)-positive breast cancer (BC) cases. Moreover, the expression of a BC-associated lncRNAs, namely DSCAM-AS1, was measured in tumoural and Paired Adjacent Non-Tumoral (PANT) tissue, as well as plasma, using Real-Time Polymerase Chain Reaction (RT-PCR). Besides, the correlations between gene expression and the clinicopathological features were analyzed. The diagnostic power of circulating DSCAM-AS1 in BC was estimated using the Area Under the Curve (AUC) value. Furthermore, we studied the DSCAM-AS1 associated with the network of competitive endogenous RNA (ceRNA) in BC using the literature review and in silico analysis. We found a significant increase in the expression levels of lncRNA in the tumour (P < 0.001) and in plasma (P < 0.001) of ER-positive BC patients. The sensitivity and specificity of DSCAM-AS1 in plasma for detection of BC from healthy controls were 100 and 97%, respectively (AUC = 0.98, P < 0.001). Accordingly, we suggest an elevated level of circulating DSCAM-AS1 as a candidate biomarker of ER-positive BC patients. Moreover, perturbation of DSCAM-AS1, as a ceRNA, acts in the tumor progression and drug resistance by affecting different cell signaling.

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Abbreviations

BC:

Breast cancer

ceRNA:

Competing endogenous RNA

DSCAM-AS1:

Down syndrome cell adhesion molecule anti-sense 1

EMT:

Epidermal-mesenchymal transition

ER:

Estrogen receptor

lncRNAs:

Long noncoding RNAs

References

  1. Moradi M-T, Hatami R, Rahimi Z (2020) Circulating CYTOR as a potential biomarker in breast cancer. International Journal of Molecular and Cellular Medicine (IJMCM) 9 (1):0–0

  2. Elmore JG, Armstrong K, Lehman CD, Fletcher SW (2005) Screening for breast cancer Jama 293(10):1245–1256

    CAS  PubMed  Google Scholar 

  3. Molina R, Barak V, van Dalen A, Duffy MJ, Einarsson R, Gion M, Goike H, Lamerz R, Nap M, Sölétormos G (2005) Tumor markers in breast cancer–European Group on Tumor Markers recommendations. Tumor Biology 26(6):281–293

    Article  Google Scholar 

  4. Marić P, Ozretić P, Levanat S, Orešković S, Antunac K, Beketić-Orešković L (2011) Tumor markers in breast cancer–evaluation of their clinical usefulness. Collegium antropologicum 35(1):241–247

    PubMed  Google Scholar 

  5. Qiu M-T, Hu J-W, Yin R, Xu L (2013) Long noncoding RNA: an emerging paradigm of cancer research. Tumor Biology 34(2):613–620

    Article  CAS  Google Scholar 

  6. Spizzo R, Almeida MIe, Colombatti A, Calin GA, (2012) Long non-coding RNAs and cancer: a new frontier of translational research? Oncogene 31(43):4577

    Article  CAS  Google Scholar 

  7. Liu H, Zhang Z, Wu N, Guo H, Zhang H, Fan D, Nie Y, Liu Y (2018) Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals functional lncRNAs in gastric cancer. Genes 9(6):303

    Article  Google Scholar 

  8. Tay Y, Rinn J, Pandolfi PP (2014) The multilayered complexity of ceRNA crosstalk and competition. Nature 505(7483):344

    Article  CAS  Google Scholar 

  9. Cerk S, Schwarzenbacher D, Adiprasito JB, Stotz M, Hutterer GC, Gerger A, Ling H, Calin GA, Pichler M (2016) Current status of long non-coding RNAs in human breast cancer. Int J Mol Sci 17(9):1485

    Article  Google Scholar 

  10. Badve S, Turbin D, Thorat MA, Morimiya A, Nielsen TO, Perou CM, Dunn S, Huntsman DG, Nakshatri H (2007) FOXA1 expression in breast cancer—correlation with luminal subtype A and survival. Clin Cancer Res 13(15):4415–4421

    Article  CAS  Google Scholar 

  11. Miano V, Ferrero G, Rosti V, Manitta E, Elhasnaoui J, Basile G, De Bortoli M (2018) Luminal lncRNAs regulation by ERα-controlled enhancers in a ligand-independent manner in breast cancer cells. Int J Mol Sci 19(2):593

    Article  Google Scholar 

  12. Deroo BJ, Korach KS (2006) Estrogen receptors and human disease. J Clin Investig 116(3):561–570

    Article  CAS  Google Scholar 

  13. Chumsri S, Howes T, Bao T, Sabnis G, Brodie A (2011) Aromatase, aromatase inhibitors, and breast cancer. The Journal of Steroid Biochemistry and Molecular BIOLOGY 125(1–2):13–22

    Article  CAS  Google Scholar 

  14. Sun W, Li AQ, Zhou P, Jiang YZ, Jin X, Liu YR, Guo YJ, Yang WT, Shao ZM, Xu XE (2018) DSCAM-AS 1 regulates the G1/S cell cycle transition and is an independent prognostic factor of poor survival in luminal breast cancer patients treated with endocrine therapy. Cancer Med 7(12):6137–6146

    Article  CAS  Google Scholar 

  15. Li D, Li J (2016) Association of miR-34a-3p/5p, miR-141-3p/5p, and miR-24 in decidual natural killer cells with unexplained recurrent spontaneous abortion. Med Sci Monit 22:922

    Article  CAS  Google Scholar 

  16. Paraskevopoulou MD, Vlachos IS, Karagkouni D, Georgakilas G, Kanellos I, Vergoulis T, Zagganas K, Tsanakas P, Floros E, Dalamagas T (2015) DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts. Nucleic Acids Res 44(D1):D231–D238

    Article  Google Scholar 

  17. Wong N, Wang X (2014) miRDB: an online resource for microRNA target prediction and functional annotations. Nucleic Acids Res 43(D1):D146–D152

    Article  Google Scholar 

  18. Liu W, Wang X (2019) Prediction of functional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biol 20(1):18

    Article  CAS  Google Scholar 

  19. Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, Koplev S, Jenkins SL, Jagodnik KM, Lachmann A (2016) Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 44(W1):W90–W97

    Article  CAS  Google Scholar 

  20. Pillai MM, Gillen AE, Yamamoto TM, Kline E, Brown J, Flory K, Hesselberth JR, Kabos P (2014) HITS-CLIP reveals key regulators of nuclear receptor signaling in breast cancer. Breast Cancer Res Treat 146(1):85–97

    Article  CAS  Google Scholar 

  21. Ma Y, Bu D, Long J, Chai W, Dong J (2019) LncRNA DSCAM-AS1 acts as a sponge of miR-137 to enhance Tamoxifen resistance in breast cancer. J Cell Physiol 234(3):2880–2894

    Article  CAS  Google Scholar 

  22. Liang WH, Li N, Yuan ZQ, Qian XL, Wang ZH (2018) DSCAM‐AS1 promotes tumor growth of breast cancer by reducing miR‐204‐5p and up‐regulating RRM2. Molecular Carcinogenesis

  23. Xu N, Chen F, Wang F, Lu X, Wang X, Lv M, Lu C (2015) Clinical significance of high expression of circulating serum lncRNA RP11–445H22. 4 in breast cancer patients: a Chinese population-based study. Tumor Biology 36 (10):7659–7665

  24. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet 15(1):7

    Article  CAS  Google Scholar 

  25. Zhao Y, Guo Q, Chen J, Hu J, Wang S, Sun Y (2014) Role of long non-coding RNA HULC in cell proliferation, apoptosis and tumor metastasis of gastric cancer: a clinical and in vitro investigation. Oncol Rep 31(1):358–364

    Article  CAS  Google Scholar 

  26. Zhang E-B, Han L, Yin D-D, Kong R, De W, Chen J (2014) c-Myc-induced, long, noncoding H19 affects cell proliferation and predicts a poor prognosis in patients with gastric cancer. Med Oncol 31(5):914

    Article  Google Scholar 

  27. Yang XR, Chang-Claude J, Goode EL, Couch FJ, Nevanlinna H, Milne RL, Gaudet M, Schmidt MK, Broeks A, Cox A (2010) Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst 103(3):250–263

    Article  Google Scholar 

  28. Miano V, Ferrero G, Reineri S, Caizzi L, Annaratone L, Ricci L, Cutrupi S, Castellano I, Cordero F, De Bortoli M (2016) Luminal long non-coding RNAs regulated by estrogen receptor alpha in a ligand-independent manner show functional roles in breast cancer. Oncotarget 7(3):3201

    Article  Google Scholar 

  29. Xu S, Kong D, Chen Q, Ping Y, Pang D (2017) Oncogenic long noncoding RNA landscape in breast cancer. Molecular Cancer 16(1):129

    Article  Google Scholar 

  30. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell 146(3):353–358

    Article  CAS  Google Scholar 

  31. Moradi MT, Fallahi H, Rahimi Z (2019) Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation. J Cell Biochem 120(3):3339–3352

    Article  CAS  Google Scholar 

  32. Cortés J, Im S-A, Holgado E, Perez-Garcia JM, Schmid P, Chavez-MacGregor M (2017) The next era of treatment for hormone receptor-positive, HER2-negative advanced breast cancer: triplet combination-based endocrine therapies. Cancer Treat Rev 61:53–60

    Article  Google Scholar 

  33. Leivonen S-K, Rokka A, Östling P, Kohonen P, Corthals GL, Kallioniemi O, Perälä M (2011) Identification of miR-193b targets in breast cancer cells and systems biological analysis of their functional impact. Mol Cell Proteomics 110:005322

    Google Scholar 

  34. Lettlova S, Brynychova V, Blecha J, Vrana D, Vondrusova M, Soucek P, Truksa J (2018) MiR-301a-3p Suppresses estrogen signaling by directly inhibiting ESR1 in ERα positive breast Cancer. Cell Physiol Biochem 46(6):2601–2615

    Article  CAS  Google Scholar 

  35. Ljepoja B, García-Roman J, Sommer A-K, Wagner E, Roidl A (2019) MiRNA-27a sensitizes breast cancer cells to treatment with Selective estrogen receptor modulators. The Breast 43:31–38

    Article  Google Scholar 

  36. Li X, Mertens-Talcott SU, Zhang S, Kim K, Ball J, Safe S (2010) MicroRNA-27a indirectly regulates estrogen receptor α expression and hormone responsiveness in MCF-7 breast cancer cells. Endocrinology 151(6):2462–2473

    Article  CAS  Google Scholar 

  37. Ma F, Zhang J, Zhong L, Wang L, Liu Y, Wang Y, Peng L, Guo B (2014) Upregulated microRNA-301a in breast cancer promotes tumor metastasis by targeting PTEN and activating Wnt/β-catenin signaling. Gene 535(2):191–197

    Article  CAS  Google Scholar 

  38. Wei H, Cui R, Bahr J, Zanesi N, Luo Z, Meng W, Liang G, Croce CM (2017) miR-130a deregulates PTEN and stimulates tumor growth. Can Res 0530:2017

    Google Scholar 

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Acknowledgements

We wish to show our appreciation to Dr. Sh. Mostafaei and Mr. E. Zereshki for their biostatistician consulting.

Funding

This study has been funded by Kermanshah University of Medical Sciences, Iran [Grant No. 95680].

Author information

Authors and Affiliations

  1. Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad-Taher Moradi

  2. Medical Biology Research Center, Medical School, Kermanshah University of Medical Sciences, Daneshgah Avenue, P.O. Box 67148‑69914, Kermanshah, Iran

    Mohammad-Taher Moradi & Zohreh Rahimi

  3. Bioinformatics Lab, Department of Biology, School of Sciences, Razi University, Kermanshah, Iran

    Hossein Fallahi

Authors
  1. Mohammad-Taher Moradi
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  2. Hossein Fallahi
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  3. Zohreh Rahimi
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Contributions

M-TM: Performed all experiments, analyzed the data and wrote the initial draft of the manuscript. HF: Contributed to bioinformatic analysis and revised the manuscript. ZR: Contributed to concept and design, financial support, and revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zohreh Rahimi.

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The authors declare no conflict of interest in this study.

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Moradi, MT., Fallahi, H. & Rahimi, Z. The clinical significance of circulating DSCAM-AS1 in patients with ER-positive breast cancer and construction of its competitive endogenous RNA network. Mol Biol Rep 47, 7685–7697 (2020). https://doi.org/10.1007/s11033-020-05841-5

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  • DOI: https://doi.org/10.1007/s11033-020-05841-5

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