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Sirt1 antisense transcript is down-regulated in human tumors

  • Neda Mokhberian
  • Seyed Mahmoud Hashemi
  • Vahid Jajarmi
  • Mohamad Eftekhary
  • Ameneh Koochaki
  • Hossein GhanbarianEmail author
Original Article

Abstract

Natural antisense transcripts (NATs) have recently been associated with the development of human cancers. Recent studies have shown that a natural antisense transcript (NAT) is present in Sirt1 gene which encodes a NAD-dependent deacetylase. Interestingly, expression of Sirt1 mRNA changes during development and progression of human cancers. However, it remains unclear to what extent Sirt1 antisense transcript (AS) may contribute to changes in the expression of Sirt1 mRNA. To determine this, we used quantitative measurement of RNA to reveal relationship between Sirt1 mRNA and Sirt1-AS across human cancer tissues, cell lines and stem cells. While Sirt1 mRNA level was increased in cancer cell lines and cancer tissues, the expression level of Sirt1-AS was lower in cancers compared to controls. This inverse correlation was observed in the expression of Sirt1 sense and antisense transcripts in normal and cancer tissues suggesting a functional role for Sirt1-AS in regulation of Sirt1 mRNA.

Keywords

Sirt1 Natural antisense transcript Human tumor Cancer cell line Stem cell 

Notes

Acknowledgements

We would like to thank the Cellular and Molecular Biology Research Center, Tehran, Iran for their kind cooperation in providing materials and equipment.

Funding

This work was supported by research grants of Iran National Science Foundation (INSF), Tehran (96008781), and research grants of Shahid Beheshti University of Medical Sciences, Tehran, Iran (15769). We would like to thank the Cellular and Molecular Biology Research Center, Tehran, Iran for their kind cooperation in providing materials and equipment.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest. The manuscript contains only original unpublished work and is not being submitted for publication elsewhere.

Ethical approval

All procedures performed in the study were in accordance with the ethical standards of the Ethics Committee at the Iran National Science Foundation (INSF) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants.

Supplementary material

11033_2019_4687_MOESM1_ESM.docx (14 kb)
Supplementary material 1 (DOCX 13 KB)

References

  1. 1.
    Abasi M, Bazi Z, Mohammadi-Yeganeh S, Soleimani M, Haghpanah V, Zargami N, Ghanbarian H (2016) 7SK small nuclear RNA transcription level down-regulates in human tumors and stem cells. Med Oncol 33(11):128Google Scholar
  2. 2.
    Abasi M, Kohram F, Fallah P, Arashkia A, Soleimani M, Zarghami N, Ghanbarian H (2017) Differential maturation of miR-17 ~ 92 cluster members in human cancer cell lines. Appl Biochem Biotechnol 182(4):1540–1547Google Scholar
  3. 3.
    Keramati F, Seyedjafari E, Fallah P, Soleimani M, Ghanbarian H (2015) 7SK small nuclear RNA inhibits cancer cell proliferation through apoptosis induction. Tumour Biol 36(4):2809–2814Google Scholar
  4. 4.
    Huang T, Alvarez A, Hu B, Cheng S-Y (2013) Noncoding RNAs in cancer and cancer stem cells. Chin J Cancer 32(11):582Google Scholar
  5. 5.
    Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159Google Scholar
  6. 6.
    Kohram F, Fallah P, Shamsara M, Bolandi Z, Rassoulzadegan M, Soleimani M, Ghanbarian H (2018) Cell type-dependent functions of microRNA-92a. J Cell Biochem 119(7):5798–5804Google Scholar
  7. 7.
    Katayama S, Tomaru Y, Kasukawa T, Waki K, Nakanishi M, Nakamura M, Nishida H, Yap C, Suzuki M, Kawai J (2005) Antisense transcription in the mammalian transcriptome. Science 309(5740):1564–1566Google Scholar
  8. 8.
    Ghanbarian H, Wagner N, Michiels J-F, Cuzin F, Wagner K-D, Rassoulzadegan M (2017) Small RNA-directed epigenetic programming of embryonic stem cell cardiac differentiation. Sci Rep 7:41799Google Scholar
  9. 9.
    Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10:637Google Scholar
  10. 10.
    Pelechano V, Steinmetz LM (2013) Gene regulation by antisense transcription. Nat Rev Genet 14:880Google Scholar
  11. 11.
    Ghanbarian H, Grandjean V, Cuzin F, Rassoulzadegan M (2011) A network of regulations by small non-coding RNAs: the P-TEFb kinase in development and pathology. Front Genet 2:95Google Scholar
  12. 12.
    Modarresi F, Faghihi MA, Lopez-Toledano MA, Fatemi RP, Magistri M, Brothers SP, van der Brug MP, Wahlestedt C (2012) Inhibition of natural antisense transcripts in vivo results in gene-specific transcriptional upregulation. Nat Biotechnol 30:453Google Scholar
  13. 13.
    Yelin R, Dahary D, Sorek R, Levanon EY, Goldstein O, Shoshan A, Diber A, Biton S, Tamir Y, Khosravi R, Nemzer S, Pinner E, Walach S, Bernstein J, Savitsky K, Rotman G (2003) Widespread occurrence of antisense transcription in the human genome. Nat Biotechnol 21:379Google Scholar
  14. 14.
    Balbin OA, Malik R, Dhanasekaran SM, Prensner JR, Cao X, Wu Y-M, Robinson D, Wang R, Chen G, Beer DG (2015) The landscape of antisense gene expression in human cancers. Genome Res 25(7):1068–1079Google Scholar
  15. 15.
    Bertozzi D, Iurlaro R, Sordet O, Marinello J, Zaffaroni N, Capranico G (2011) Characterization of novel antisense HIF-1α transcripts in human cancers. Cell Cycle 10(18):3189–3197Google Scholar
  16. 16.
    Su W-Y, Li J-T, Cui Y, Hong J, Du W, Wang Y-C, Lin Y-W, Xiong H, Wang J-L, Kong X, Gao Q-Y, Wei L-P, Fang J-Y (2012) Bidirectional regulation between WDR83 and its natural antisense transcript DHPS in gastric cancer. Cell Res 22:1374Google Scholar
  17. 17.
    Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 23(12):2369–2380Google Scholar
  18. 18.
    Herranz D, Muñoz-Martin M, Cañamero M, Mulero F, Martinez-Pastor B, Fernandez-Capetillo O, Serrano M (2010) Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. Nat Commun 1:3Google Scholar
  19. 19.
    North BJ, Verdin E (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol 5(5):224Google Scholar
  20. 20.
    Huffman DM, Grizzle WE, Bamman MM, Kim J-s, Eltoum IA, Elgavish A, Nagy TR (2007) SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res 67(14):6612–6618Google Scholar
  21. 21.
    Bae HJ, Noh JH, Kim JK, Eun JW, Jung KH, Kim MG, Chang YG, Shen Q, Kim SJ, Park WS, Lee JY, Nam SW (2013) MicroRNA-29c functions as a tumor suppressor by direct targeting oncogenic SIRT1 in hepatocellular carcinoma. Oncogene 33:2557Google Scholar
  22. 22.
    Wang Y, Pang W-J, Wei N, Xiong Y, Wu W-J, Zhao C-Z, Shen Q-W, Yang G-S (2014) Identification, stability and expression of Sirt1 antisense long non-coding RNA. Gene 539(1):117–124Google Scholar
  23. 23.
    Yamakuchi M, Ferlito M, Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 105(36):13421–13426Google Scholar
  24. 24.
    Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21:1253Google Scholar
  25. 25.
    Bazi Z, Bertacchi M, Abasi M, Mohammadi-Yeganeh S, Soleimani M, Wagner N, Ghanbarian H (2018) Rn7SK small nuclear RNA is involved in neuronal differentiation. J Cell Biochem 119(4):3174–3182Google Scholar
  26. 26.
    Tarhriz V, Wagner KD, Masoumi Z, Molavi O, Hejazi MS, Ghanbarian H (2018) CDK9 regulates apoptosis of myoblast cells by modulation of microRNA-1 expression. J Cell Biochem 119(1):547–554Google Scholar
  27. 27.
    Faghihi MA, Modarresi F, Khalil AM, Wood DE, Sahagan BG, Morgan TE, Finch CE, St. Laurent Iii G, Kenny PJ, Wahlestedt C (2008) Expression of a noncoding RNA is elevated in Alzheimer’s disease and drives rapid feed-forward regulation of β-secretase. Nat Med 14:723Google Scholar
  28. 28.
    Yap KL, Li S, Muñoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou M-M (2010) Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 38(5):662–674Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Neda Mokhberian
    • 1
  • Seyed Mahmoud Hashemi
    • 2
    • 4
  • Vahid Jajarmi
    • 3
  • Mohamad Eftekhary
    • 1
  • Ameneh Koochaki
    • 3
  • Hossein Ghanbarian
    • 1
    • 3
    • 4
    Email author
  1. 1.Department of Biotechnology, School of Advanced Technologies in MedicineShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Department of Immunology, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Cellular and Molecular Biology Research CenterShahid 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

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