Skip to main content

Advertisement

SpringerLink
Log in

Esophageal cancer-selective expression of TRAIL mediated by MREs of miR-143 and miR-122

  • Research Article
  • Published:
Tumor Biology

Abstract

Esophageal cancer is one of the most common digestive system neoplasms and has a quite poor prognosis. TNF-related apoptosis-inducing ligand (TRAIL) induces the apoptosis in a wide range of cancer cells including esophageal cancers. However, TRAIL also activates apoptotic pathway in normal cells. To improve the specificity of TRAIL action, we employed the microRNA (miRNA) response elements (MREs) of miR-143 and miR-122 to restrict TRAIL expression mediated by an adenoviral vector (Ad-TRAIL-143-122) in esophageal cancer cells. The experiments showed that Ad-TRAIL-143-122 was able to highly express TRAIL in esophageal cancer cells, but not normal cells. The selective TRAIL expression also led to selective apoptosis in esophageal cancer cells. Ad-TRAIL-143-122 greatly reduced the viability of esophageal cancer cells without cytotoxicity to normal cells. In mice, Ad-TRAIL-143-122 suppressed the growth of esophageal cancer xenografts and protected liver from TRAIL-induced toxicity. In this study, we constructed a biologic vector that can express exogenous genes in a tumor-specific manner. This strategy can simultaneously treat cancer and prevent hepatoxicity and thus may be a promising way for esophageal cancer treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349:2241–52.

    Article  CAS  PubMed  Google Scholar 

  2. Pan G, O’Rourke K, Chinnaiyan AM, Gentz R, Ebner R, Ni J, et al. The receptor for the cytotoxic ligand trail. Science. 1997;276:111–3.

    Article  CAS  PubMed  Google Scholar 

  3. Younes M, Georgakis GV, Rahmani M, Beer D, Younes A. Functional expression of trail receptors trail-r1 and trail-r2 in esophageal adenocarcinoma. Eur J Cancer. 2006;42:542–7.

    Article  CAS  PubMed  Google Scholar 

  4. Kondo K, Yamasaki S, Inoue N, Sugie T, Teratani N, Kan T, et al. Prospective antitumor effects of the combination of tumor necrosis factor-related apoptosis-inducing ligand (trail) and cisplatin against esophageal squamous cell carcinoma. Surg Today. 2006;36:966–74.

    Article  CAS  PubMed  Google Scholar 

  5. Kim SH, Kim K, Kwagh JG, Dicker DT, Herlyn M, Rustgi AK, et al. Death induction by recombinant native trail and its prevention by a caspase 9 inhibitor in primary human esophageal epithelial cells. J Biol Chem. 2004;279:40044–52.

    Article  CAS  PubMed  Google Scholar 

  6. Zheng SJ, Wang P, Tsabary G, Chen YH. Critical roles of trail in hepatic cell death and hepatic inflammation. J Clin Invest. 2004;113:58–64.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  8. Croce CM, Calin GA. MiRNAs, cancer, and stem cell division. Cell. 2005;122:6–7.

    Article  CAS  PubMed  Google Scholar 

  9. Gu J, Wang Y, Wu X. MicroRNA in the pathogenesis and prognosis of esophageal cancer. Curr Pharm Des. 2013;19:1292–300.

    Article  CAS  PubMed  Google Scholar 

  10. Liu SG, Qin XG, Zhao BS, Qi B, Yao WJ, Wang TY, et al. Differential expression of miRNAs in esophageal cancer tissue. Oncol Lett. 2013;5:1639–42.

    PubMed Central  CAS  PubMed  Google Scholar 

  11. Wu BL, Xu LY, Du ZP, Liao LD, Zhang HF, Huang Q, et al. Li EM: miRNA profile in esophageal squamous cell carcinoma: downregulation of mir-143 and mir-145. World J Gastroenterol. 2011;17:79–88.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Liu R, Liao J, Yang M, Sheng J, Yang H, Wang Y, et al. The cluster of mir-143 and mir-145 affects the risk for esophageal squamous cell carcinoma through co-regulating fascin homolog 1. PLoS One. 2012;7:e33987.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Ni Y, Meng L, Wang L, Dong W, Shen H, Wang G, et al. MicroRNA-143 functions as a tumor suppressor in human esophageal squamous cell carcinoma. Gene. 2013;517:197–204.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang W, Cai R, Luo J, Wang Y, Cui Q, Wei X, et al. The oncolytic adenovirus targeting to tert and rb pathway induced specific and potent anti-tumor efficacy in vitro and in vivo for hepatocellular carcinoma. Cancer Biol Ther. 2007;6:1726–32.

    Article  CAS  PubMed  Google Scholar 

  15. Liu J, Ma L, Li C, Zhang Z, Yang G, Zhang W. Tumor-targeting trail expression mediated by miRNA response elements suppressed growth of uveal melanoma cells. Mol Oncol. 2013;7:1043–55.

    Article  CAS  PubMed  Google Scholar 

  16. Bo Y, Guo G, Yao W. MiRNA-mediated tumor specific delivery of trail reduced glioma growth. J Neurooncol. 2013;112:27–37.

    Article  CAS  PubMed  Google Scholar 

  17. Zhao Y, Li Y, Wang L, Yang H, Wang Q, Qi H, et al. MicroRNA response elements-regulated trail expression shows specific survival-suppressing activity on bladder cancer. J Exp Clin Cancer Res. 2013;32:10.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Hu J, Xu Y, Hao J, Wang S, Li C, Meng S. Mir-122 in hepatic function and liver diseases. Protein Cell. 2012;3:364–71.

    Article  CAS  PubMed  Google Scholar 

  19. Ma L, Liu J, Shen J, Liu L, Wu J, Li W, et al. Expression of mir-122 mediated by adenoviral vector induces apoptosis and cell cycle arrest of cancer cells. Cancer Biol Ther. 2010;9:554–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by The youth innovation fund of the First Affiliated Hospital of Zhengzhou University.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, 450052, China

    Kun Zhou & Song Zhao

  2. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Yan Yan

Authors
  1. Kun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Song Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Song Zhao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, K., Yan, Y. & Zhao, S. Esophageal cancer-selective expression of TRAIL mediated by MREs of miR-143 and miR-122 . Tumor Biol. 35, 5787–5795 (2014). https://doi.org/10.1007/s13277-014-1768-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1768-5

Keywords

Search

Navigation