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Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation

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Abstract

Long non-coding RNAs are manifested as a new paradigm of molecular effectors in a wide range of human diseases. Human SOX2 overlapping transcript (SOX2OT) gene can generate six lncRNA transcript variants which are functionally assumed to be correlated with cellular differentiation and carcinogenesis. However, the circumstances determining expressional and functional differences between SOX2OT transcript variants remain to be explored. Here, we studied the expression of all SOX2OT transcript variants specifically in five human cancer cell lines by real-time RT-PCR. Changes of the new SOX2OT transcript variants expression were measured during the NT2 teratocarcinoma cell line neuronal-like differentiation and were compared to pluripotency regulators, SOX2 and OCT4A gene expressions. Surprisingly, we identified two new SOX2OT transcripts, named SOX2OT-7, SOX2OT-8 which lack exon 8. We discovered that beside active proximal and distal SOX2OT promoters, different cancer cell lines express high levels of some SOX2OT transcript variants differentially by alternative splicing. Significantly, both SOX2OT-7 and SOX2OT-8 are highly expressed in human cancer cell lines coinciding with SOX2, one of the pluripotency regulators. Our results revealed that SOX2OT-7 is almost the most abundant form of SOX2OT transcript variants in the examined cancer cell lines particularly in NT2 teratocarcinoma cell line where its expression falls upon neuronal-like differentiation similar to SOX2 and OCT4A. We suggest that at least some of SOX2OT transcripts are significantly associated with cancer and stem cell related pathways.

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References

  1. Birney E, Stamatoyannopoulos JA, Dutta A, Guigó R, Gingeras TR, Margulies EH, Weng Z, Snyder M, Dermitzakis ET, Thurman RE (2007) Identification and analysis of functional elements in 1 % of the human genome by the ENCODE pilot project. Nature 447(7146):799–816

    Article  CAS  PubMed  Google Scholar 

  2. Carninci P, Kasukawa T, Katayama S, Gough J, Frith M, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C (2005) The transcriptional landscape of the mammalian genome. Science 309(5740):1559–1563

    Article  CAS  PubMed  Google Scholar 

  3. Consortium EP (2004) The ENCODE (ENCyclopedia of DNA elements) project. Science 306(5696):636–640

    Article  Google Scholar 

  4. Consortium IHGS (2004) Finishing the euchromatic sequence of the human genome. Nature 431(7011):931–945

    Article  Google Scholar 

  5. Amaral PP, Mattick JS (2008) Noncoding RNA in development. Mamm Genome 19(7–8):454–492

    Article  CAS  PubMed  Google Scholar 

  6. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science 316(5830):1484–1488

    Article  CAS  PubMed  Google Scholar 

  7. Ponting CP, Oliver PL, Reik W (2009) Evolution and functions of long noncoding RNAs. Cell 136(4):629–641

    Article  CAS  PubMed  Google Scholar 

  8. Chen L-L, Carmichael GG (2010) Decoding the function of nuclear long non-coding RNAs. Curr Opin Cell Biol 22(3):357–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Kaikkonen MU, Lam MT, Glass CK (2011) Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res 90(3):430–440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Taft RJ, Pang KC, Mercer TR, Dinger M, Mattick JS (2010) Non-coding RNAs: regulators of disease. J Pathol 220(2):126–139

    Article  CAS  PubMed  Google Scholar 

  11. Wang X, Song X, Glass CK, Rosenfeld MG (2011) The long arm of long noncoding RNAs: roles as sensors regulating gene transcriptional programs. Cold Spring Harb Perspect Biol 3(1):a003756

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wilusz JE, Sunwoo H, Spector DL (2009) Long noncoding RNAs: functional surprises from the RNA world. Genes Dev 23(13):1494–1504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fejes-Toth K, Sotirova V, Sachidanandam R, Assaf G, Hannon GJ, Kapranov P, Foissac S, Willingham AT, Duttagupta R, Dumais E (2009) Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature 457(7232):1028–1032

    Article  CAS  PubMed Central  Google Scholar 

  14. Fantes J, Ragge NK, Lynch S-A, McGill NI, Collin JRO, Howard-Peebles PN, Hayward C, Vivian AJ, Williamson K, van Heyningen V (2003) Mutations in SOX2 cause anophthalmia. Nat Genet 33(4):461–463

    Article  CAS  PubMed  Google Scholar 

  15. Andrew T, Maniatis N, Carbonaro F, Liew SM, Lau W, Spector TD, Hammond CJ (2008) Identification and replication of three novel myopia common susceptibility gene loci on chromosome 3q26 using linkage and linkage disequilibrium mapping. PLoS Genet 4(10):e1000220

    Article  PubMed  PubMed Central  Google Scholar 

  16. Shahryari A, Rafiee MR, Fouani Y, Oliae NA, Samaei NM, Shafiee M, Semnani S, Vasei M, Mowla SJ (2014) Two novel splice variants of SOX2OT, SOX2OT‐S1, and SOX2OT‐S2 are coupregulated with SOX2 and OCT4 in esophageal squamous cell carcinoma. Stem Cells 32(1):126–134

    Article  CAS  PubMed  Google Scholar 

  17. Amaral PP, Neyt C, Wilkins SJ, Askarian-Amiri ME, Sunkin SM, Perkins AC, Mattick JS (2009) Complex architecture and regulated expression of the Sox2ot locus during vertebrate development. RNA 15(11):2013–2027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hussenet T, Dali S, Exinger J, Monga B, Jost B, Dembelé D, Martinet N, Thibault C, Huelsken J, Brambilla E (2010) SOX2 is an oncogene activated by recurrent 3q26.3 amplifications in human lung squamous cell carcinomas. PLoS One 5(1):e8960

    Article  PubMed  PubMed Central  Google Scholar 

  19. Askarian-Amiri ME, Seyfoddin V, Smart CE, Wang J, Kim JE, Hansji H, Baguley BC, Finlay GJ, Leung EY (2014) Emerging role of long non-coding RNA SOX2OT in SOX2 regulation in breast cancer. PLoS One 9(7):e102140

    Article  PubMed  PubMed Central  Google Scholar 

  20. Hou Z, Zhao W, Zhou J, Shen L, Zhan P, Xu C, Chang C, Bi H, Zou J, Yao X (2014) A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. Int J Biochem Cell Biol 53:380–388

    Article  CAS  PubMed  Google Scholar 

  21. Atlasi Y, Mowla SJ, Ziaee SA, Gokhale PJ, Andrews PW (2008) OCT4 spliced variants are differentially expressed in human pluripotent and nonpluripotent cells. Stem Cells 26(12):3068–3074

    Article  CAS  PubMed  Google Scholar 

  22. Mattick JS, Makunin IV (2006) Non-coding RNA. Hum Mol Genet 15(suppl 1):R17–R29

    Article  CAS  PubMed  Google Scholar 

  23. Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci 105(2):716–721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shahryari A, Jazi MS, Samaei NM, Mowla SJ (2015) Long non-coding RNA SOX2OT: expression signature, splicing patterns, and emerging roles in pluripotency and tumorigenesis. Front Genet 6:196

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was part of a PhD thesis financially supported by Golestan University of Medical Science (grant number: 92041130).

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Authors and Affiliations

  1. Department of Molecular Medicine, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, Gorgan, Iran

    Marie Saghaeian Jazi

  2. Stem Cell Research Center, Golestan University of Medical Sciences, Gorgan, Iran

    Nader Mansour Samaei

  3. Department of Human Genetics, Faculty of Advanced Medical Technologies, Golestan University of Medical Sciences, P.O.Box 4934174611, Gorgan, Iran

    Nader Mansour Samaei

  4. Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mostafa Ghanei

  5. Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohammad Behgam Shadmehr

  6. Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Seyed Javad Mowla

Authors
  1. Marie Saghaeian Jazi
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  2. Nader Mansour Samaei
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  3. Mostafa Ghanei
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  4. Mohammad Behgam Shadmehr
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  5. Seyed Javad Mowla
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Correspondence to Nader Mansour Samaei.

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Saghaeian Jazi, M., Samaei, N.M., Ghanei, M. et al. Identification of new SOX2OT transcript variants highly expressed in human cancer cell lines and down regulated in stem cell differentiation. Mol Biol Rep 43, 65–72 (2016). https://doi.org/10.1007/s11033-015-3939-x

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  • DOI: https://doi.org/10.1007/s11033-015-3939-x

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