Skip to main content
Log in

Down-Regulation of miR-27a Might Reverse Multidrug Resistance of Esophageal Squamous Cell Carcinoma

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

So far, the miRNAs involved in multidrug resistance of esophageal cancer have not been reported.

Aims and Methods

Here we have firstly investigated the roles of miR-27a in multidrug resistance of esophageal squamous cell carcinoma using MTT assay, flow cytometry assay, and reporter gene assay, etc.

Results

Down-regulation of miR-27a could confer sensitivity of both P-glycoprotein-related and P-glycoprotein-non-related drugs on esophageal cancer cells, and might promote ADR-induced apoptosis, accompanied by increased accumulation and decreased releasing amount of ADR. Down-regulation of miR-27a could significantly decrease the expression of P-glycoprotein, Bcl-2, and the transcription of the multidrug resistance gene 1, but up-regulate the expression of Bax.

Conclusions

MiR-27a might play important roles in multidrug resistance of esophageal cancer. The further study of the biological functions of miR-27a might be helpful for developing possible strategies to treat esophageal cancer.

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

Access this article

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

Similar content being viewed by others

Abbreviations

VCR:

Vincristine

ADR:

Adriamycin

5-Flu:

5-Fluorouracil

CDDP:

Cisplatin

FCM:

Flow cytometry

miRNA:

microRNA

MTT:

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

MDR:

Multidrug resistance

P-gp:

P-glycoprotein

MRP:

Multidrug resistance-associated protein

References

  1. Yan S, Zhou C, Lou X, et al. PTTG overexpression promotes lymph node metastasis in human esophageal squamous cell carcinoma. Cancer Res. 2009;69:3283–3290.

    Article  CAS  PubMed  Google Scholar 

  2. Winter J, Jung S, Keller S, et al. Many roads to maturity: MicroRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228–234.

    Article  CAS  PubMed  Google Scholar 

  3. Lakshmipathy U, Hart RP. Concise review: MicroRNA expression in multipotent mesenchymal stromal cells. Stem Cells. 2008;26:356–363.

    Article  CAS  PubMed  Google Scholar 

  4. Tsai WC, Hsu PW, Lai TC, et al. MicroRNA-122, a tumor suppressor microRNA that regulates intrahepatic metastasis of hepatocellular carcinoma. Hepatology. 2009;49:1571–1582.

    Article  CAS  PubMed  Google Scholar 

  5. Cordes KR, Srivastava D. MicroRNA regulation of cardiovascular development. Circ Res. 2009;104:724–732.

    Article  CAS  PubMed  Google Scholar 

  6. Chen Y, Stallings RL. Differential patterns of microRNA expression in neuroblastoma are correlated with prognosis, differentiation, and apoptosis. Cancer Res. 2007;67:976–983.

    Article  CAS  PubMed  Google Scholar 

  7. Calin GA, Ferracin M, Cimmino A, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353:1793–1801.

    Article  CAS  PubMed  Google Scholar 

  8. Hong L, Piao Y, Han Y, et al. Zinc ribbon domain-containing 1 (ZNRD1) mediates multidrug resistance of leukemia cells through regulation of P-glycoprotein and Bcl-2. Mol Cancer Ther. 2005;4:1936–1942.

    Article  CAS  PubMed  Google Scholar 

  9. Hong L, Qiao T, Han Y, et al. ZNRD1 mediates resistance of gastric cancer cells to methotrexate by regulation of IMPDH2 and Bcl-2. Biochem Cell Biol. 2006;84:199–206.

    Article  CAS  PubMed  Google Scholar 

  10. Fogel M, Gutwein P, Mechtersheimer S, et al. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet. 2003;362:869–875.

    Article  CAS  PubMed  Google Scholar 

  11. Ji J, Zhang J, Huang G, et al. Over-expressed microRNA-27a and 27b influence fat accumulation and cell proliferation during rat hepatic stellate cell activation. FEBS Lett. 2009;583:759–766.

    Article  CAS  PubMed  Google Scholar 

  12. Ben-Ami O, Pencovich N, Lotem J, et al. A regulatory interplay between miR-27a and Runx1 during megakaryopoiesis. Proc Natl Acad Sci USA. 2009;106:238–243.

    Article  CAS  PubMed  Google Scholar 

  13. Liu T, Tang H, Lang Y, et al. MicroRNA-27a functions as an oncogene in gastric adenocarcinoma by targeting prohibitin. Cancer Lett. 2009;273:233–242.

    Article  CAS  PubMed  Google Scholar 

  14. Arisawa T, Tahara T, Shibata T, et al. A polymorphism of microRNA 27a genome region is associated with the development of gastric mucosal atrophy in Japanese male subjects. Dig Dis Sci. 2007;52:1691–1697.

    Article  CAS  PubMed  Google Scholar 

  15. Hong L, Wang J, Han Y, et al. Reversal of multidrug resistance of vincristine-resistant gastric adenocarcinoma cells through up-regulation of DARPP-32. Cell Biol Int. 2007;31(9):1010–1015.

    Article  CAS  PubMed  Google Scholar 

  16. Kang MH, Reynolds CP. Bcl-2 inhibitors: Targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res. 2009;15(4):1126–1132.

    Article  CAS  PubMed  Google Scholar 

  17. Del Poeta G, Bruno A, Del Principe MI, et al. Deregulation of the mitochondrial apoptotic machinery and development of molecular targeted drugs in acute myeloid leukemia. Curr Cancer Drug Targets. 2008;8(3):207–222.

    Article  CAS  PubMed  Google Scholar 

  18. Asakura T, Ohkawa K. Chemotherapeutic agents that induce mitochondrial apoptosis. Curr Cancer Drug Targets. 2004;4(7):577–590.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by grants from the National Scientific Foundation of China (30770958 and 30871141).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Hongwei Zhang or Liu Hong.

Additional information

Hongwei Zhang, Mengbin Li, Yu Han, and Liu Hong contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, H., Li, M., Han, Y. et al. Down-Regulation of miR-27a Might Reverse Multidrug Resistance of Esophageal Squamous Cell Carcinoma. Dig Dis Sci 55, 2545–2551 (2010). https://doi.org/10.1007/s10620-009-1051-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-009-1051-6

Keywords

Navigation