A novel natural antisense transcript at human SOX9 locus is down-regulated in cancer and stem cells

  • Mohamad Eftekhary
  • Samira Mohammadi-Yeganeh
  • Zohreh Bolandi
  • Seyed Mahmoud Hashemi
  • Neda Mokhberian
  • Kazem SharifiEmail author
  • Hossein GhanbarianEmail author
Original Research Paper



SOX9 is a key transcription factor with important roles in regulating proliferation and differentiation of various cell types. Dysregulation of SOX9 expression has been involved with pathogenesis of different developmental, degenerative, and neoplastic disorders. Natural antisense transcripts (NATs) are long non-coding RNAs with increasing significance in regulation of gene expression. However, the presence of a NAT at SOX9 locus has been so far unclear.


We detected a natural antisense transcript at SOX9 locus (SOX9-NAT) through strand-specific RT-PCR. In contrast to SOX9 sense RNA (mRNA), SOX9-NAT was down-regulated in cancer tissues and cell lines compared with their normal counterparts. In addition, reciprocal to SOX9 mRNA, SOX9-NAT was also down-regulated in human embryonic stem cells in comparison with human fibroblasts in vitro.


The negative correlation between SOX9 mRNA and SOX9-NAT was confirmed by analyzing qPCR data, as well as RNA-Seq datasets of several human cancers. Our data suggest a functional role for SOX9-NAT in the regulation of SOX9 mRNA as a potential target in cancer treatment and regenerative medicine.


SOX9 Natural antisense transcript Cancer Gene expression regulation Stem cells 



This work was financially supported by a Shahid Beheshti University of Medical Sciences, Tehran, Iran (grant number: 14325). Our team appreciates the cellular and molecular biology research center, Tehran, Iran for providing space and facilities.

Author contributions

M.E., S.M.H., K.S., and H.G. comprehended and designed the study. M.E., S.M.H., N.M., Z.B., H.G., and S.M.-Y. performed the experiments. M.E., K.S., S.M.-Y., and H.G. analyzed the data and construed the results. M.E., N.M., Z.B., and H.G. prepared the manuscript. M.E., K.S., and H.G. reviewed during the preparation of manuscript and revised the manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest concerning the publication of this paper.

Ethical approval

All experiments performed in this study were in agreement with the ethical standards of the Ethics Committee at the Shahid Beheshti University of Medical Sciences and with the 1964 Helsinki declaration.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Mohamad Eftekhary
    • 1
  • Samira Mohammadi-Yeganeh
    • 1
    • 2
  • Zohreh Bolandi
    • 2
  • Seyed Mahmoud Hashemi
    • 3
    • 4
    • 5
  • Neda Mokhberian
    • 2
  • Kazem Sharifi
    • 1
    • 2
    Email author
  • Hossein Ghanbarian
    • 1
    • 5
    Email author
  1. 1.Department of Biotechnology, School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Cellular and Molecular Biology Research CenterShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Department of Immunology, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
  4. 4.Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
  5. 5.Urogenital Stem Cell Research CenterShahid Beheshti University of Medical SciencesTehranIran

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