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Sirt1 antisense transcript is down-regulated in human tumors

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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.

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References

  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):128

    Article  Google Scholar 

  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):1540–1547

    Article  CAS  Google Scholar 

  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):2809–2814

    Article  CAS  Google Scholar 

  4. Huang T, Alvarez A, Hu B, Cheng S-Y (2013) Noncoding RNAs in cancer and cancer stem cells. Chin J Cancer 32(11):582

    Article  CAS  Google Scholar 

  5. Mercer TR, Dinger ME, Mattick JS (2009) Long non-coding RNAs: insights into functions. Nat Rev Genet 10(3):155–159

    Article  CAS  Google Scholar 

  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):5798–5804

    Article  CAS  Google Scholar 

  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):1564–1566

    Article  Google Scholar 

  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 7:41799

    Article  CAS  Google Scholar 

  9. Faghihi MA, Wahlestedt C (2009) Regulatory roles of natural antisense transcripts. Nat Rev Mol Cell Biol 10:637

    Article  CAS  Google Scholar 

  10. Pelechano V, Steinmetz LM (2013) Gene regulation by antisense transcription. Nat Rev Genet 14:880

    Article  CAS  Google Scholar 

  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 2:95

    Article  Google Scholar 

  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 30:453

    Article  CAS  Google Scholar 

  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 21:379

    Article  CAS  Google Scholar 

  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):1068–1079

    Article  CAS  Google Scholar 

  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):3189–3197

    Article  CAS  Google Scholar 

  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 22:1374

    Article  CAS  Google Scholar 

  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):2369–2380

    Article  CAS  Google Scholar 

  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 1:3

    Article  Google Scholar 

  19. North BJ, Verdin E (2004) Sirtuins: Sir2-related NAD-dependent protein deacetylases. Genome Biol 5(5):224

    Article  Google Scholar 

  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):6612–6618

    Article  CAS  Google Scholar 

  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 33:2557

    Article  Google Scholar 

  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):117–124

    Article  CAS  Google Scholar 

  23. Yamakuchi M, Ferlito M, Lowenstein CJ (2008) miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 105(36):13421–13426

    Article  CAS  Google Scholar 

  24. Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21:1253

    Article  CAS  Google Scholar 

  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):3174–3182

    Article  CAS  Google Scholar 

  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):547–554

    Article  CAS  Google Scholar 

  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 14:723

    Article  CAS  Google Scholar 

  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):662–674

    Article  CAS  Google Scholar 

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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.

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Authors and Affiliations

  1. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Neda Mokhberian, Mohamad Eftekhary & Hossein Ghanbarian

  2. Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Mahmoud Hashemi

  3. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Vahid Jajarmi, Ameneh Koochaki & Hossein Ghanbarian

  4. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Seyed Mahmoud Hashemi & Hossein Ghanbarian

Authors
  1. Neda Mokhberian
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  2. Seyed Mahmoud Hashemi
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  3. Vahid Jajarmi
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  4. Mohamad Eftekhary
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  5. Ameneh Koochaki
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  6. Hossein Ghanbarian
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Correspondence to Hossein Ghanbarian.

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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.

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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.

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Mokhberian, N., Hashemi, S.M., Jajarmi, V. et al. Sirt1 antisense transcript is down-regulated in human tumors. Mol Biol Rep 46, 2299–2305 (2019). https://doi.org/10.1007/s11033-019-04687-w

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  • DOI: https://doi.org/10.1007/s11033-019-04687-w

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