Skip to main content
SpringerLink
Log in

MiR-26a regulates cell cycle and anoikis of human esophageal adenocarcinoma cells through Rb1-E2F1 signaling pathway

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Resistance to anoikis, the subtype of apoptosis induced by lack of matrix adhesion, contributes to malignant transformation and development of metastasis. MicroRNAs play key regulatory roles in tumorigenesis and metastasis. In this study, we described that miR-26a, which is usually downregulated in tumor cells, is involved in the acquisition of anoikis-resistance of human esophageal adenocarcinoma (EA) cells. Results of qRT-PCR in clinical samples showed that downregulated miR-26a expression is related to tumorigenesis and metastasis of EA. In vitro experiments determined that miR-26a directly participates in the regulation of cell cycle and anoikis of human EA OE33 cells. Further, we identified that Rb1 is the direct functional target of miR-26a, and revealed that the reduction of miR-26a expression leads to increased Rb1 protein level and thus inhibits the function of E2F1, by which it influences the phenotypes of cell cycle and anoikis. The findings we reported here presented the evidence that miR-26a may be involved in regulation of anoikis-resistance of EA cells. Targeting miR-26a may provide a novel strategy to inhibit metastasis.

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

Similar content being viewed by others

References

  1. Pohl H, Sirovich B, Welch HG et al (2010) Esophageal adenocarcinoma incidence: are we reaching the peak? Cancer Epidemiol Biomarkers Prev 19(6):1468–1470

    Article  PubMed  Google Scholar 

  2. Mariette C, Balon JM, Piessen G et al (2003) Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease. Cancer 97(7):1616–1623

    Article  PubMed  Google Scholar 

  3. Horbinski C, Mojesky C, Kyprianou N (2010) Live free or die: tales of homeless (cells) in cancer. Am J Pathol 177(3):1044–1052

    Article  PubMed  CAS  Google Scholar 

  4. Frisch SM, Screaton RA (2001) Anoikis mechanisms. Curr Opin Cell Biol 13(5):555–562

    Article  PubMed  CAS  Google Scholar 

  5. Simpson CD, Anyiwe K, Schimmer AD (2008) Anoikis resistance and tumor metastasis. Cancer Lett 272(2):177–185

    Article  PubMed  CAS  Google Scholar 

  6. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  PubMed  CAS  Google Scholar 

  7. Inui M, Martello G, Piccolo S (2010) MicroRNA control of signal transduction. Nat Rev Mol Cell Biol 11(4):252–263

    PubMed  CAS  Google Scholar 

  8. Korpal M, Kang Y (2008) The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol 5(3):115–119

    Article  PubMed  CAS  Google Scholar 

  9. Krichevsky AM, Gabriely G (2009) miR-21: a small multi-faceted RNA. J Cell Mol Med 13(1):39–53

    Article  PubMed  CAS  Google Scholar 

  10. Schafer ZT, Grassian AR, Song L et al (2009) Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 461(7260):109–113

    Article  PubMed  CAS  Google Scholar 

  11. Gros SJ, Dohrmann T, Peldschus K et al (2010) Complementary use of fluorescence and magnetic resonance imaging of metastatic esophageal cancer in a novel orthotopic mouse model. Int J Cancer 126(11):2671–2681

    PubMed  CAS  Google Scholar 

  12. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  13. Zhang YF, Li XH, Shi YQ (2011) CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53. Oncol Rep 25(4):1091–1098

    PubMed  CAS  Google Scholar 

  14. Dong LW, Yang GZ, Pan YF et al (2011) The oncoprotein p28(GANK) establishes a positive feedback loop in β-catenin signaling. Cell Res 21(8):1248–1261

    Article  PubMed  CAS  Google Scholar 

  15. Ji J, Shi J, Budhu A, Yu Z et al (2009) MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med 361(15):1437–1447

    Article  PubMed  CAS  Google Scholar 

  16. Villanueva A, Hoshida Y, Toffanin S et al (2010) New strategies in hepatocellular carcinoma: genomic prognostic markers. Clin Cancer Res 16(9):4688–4694

    Article  PubMed  CAS  Google Scholar 

  17. Ciarapica R, Russo G, Verginelli F et al (2009) Deregulated expression of miR-26a and Ezh2 in rhabdomyosarcoma. Cell Cycle 8(1):172–175

    Article  PubMed  CAS  Google Scholar 

  18. Heinzelmann J, Henning B, Sanjmyatav J et al (2011) Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol 29(3):367–373

    Article  PubMed  CAS  Google Scholar 

  19. Kota J, Chivukula RR, O’Donnell KA et al (2009) Therapeutic microRNA delivery suppresses tumorigenesis in a murine liver cancer model. Cell 137(6):1005–1017

    Article  PubMed  CAS  Google Scholar 

  20. Kim H, Huang W, Jiang X et al (2010) Integrative genome analysis reveals an oncomir/oncogene cluster regulating glioblastoma survivorship. Proc Natl Acad Sci USA 107(5):2183–2188

    Article  PubMed  CAS  Google Scholar 

  21. Du W, Searle JS (2009) The rb pathway and cancer therapeutics. Curr Drug Targets 10(7):581–589

    Article  PubMed  CAS  Google Scholar 

  22. Rogoff HA, Kowalik TF (2004) Life, death and E2F: linking proliferation control and DNA damage signaling via E2F1. Cell Cycle 3(7):845–846

    Article  PubMed  CAS  Google Scholar 

  23. Tanaka H, Matsumura I, Ezoe S et al (2002) E2F1 and c-Myc potentiate apoptosis through inhibition of NF-kappaB activity that facilitates MnSOD-mediated ROS elimination. Mol Cell 9(5):1017–1029

    Article  PubMed  CAS  Google Scholar 

  24. Chen M, Capps C, Willerson JT (2002) E2F-1 regulates nuclear factor-kappaB activity and cell adhesion: potential antiinflammatory activity of the transcription factor E2F-1. Circulation 106(21):2707–2713

    Article  PubMed  CAS  Google Scholar 

  25. Hao H, Zhou HS, McMasters KM (2009) Chemosensitization of tumor cells: inactivation of nuclear factor-kappa B associated with chemosensitivity in melanoma cells after combination treatment with E2F-1 and doxorubicin. Methods Mol Biol 542:301–313

    Article  PubMed  CAS  Google Scholar 

  26. Hwang HC, Clurman BE (2005) Cyclin E in normal and neoplastic cell cycles. Oncogene 24(17):2776–2786

    Article  PubMed  CAS  Google Scholar 

  27. Ohtani K, DeGregori J, Nevins JR (1995) Regulation of the cyclin E gene by transcription factor E2F1. Proc Natl Acad Sci USA 92(26):12146–12150

    Article  PubMed  CAS  Google Scholar 

  28. Ak P, Levine AJ (2010) p53 and NF-κB: different strategies for responding to stress lead to a functional antagonism. FASEB J 24(10):3643–3652

    Article  PubMed  CAS  Google Scholar 

  29. Sander S, Bullinger L, Wirth T (2009) Repressing the repressor: a new mode of MYC action in lymphomagenesis. Cell Cycle 8(4):556–559

    Article  PubMed  CAS  Google Scholar 

  30. Wong CF, Tellam RL (2008) MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis. J Biol Chem 283(15):9836–9843

    Article  PubMed  CAS  Google Scholar 

  31. Wu Z, Yu Q (2009) E2F1-mediated apoptosis as a target of cancer therapy. Curr Mol Pharmacol 2(2):149–160

    PubMed  CAS  Google Scholar 

  32. Mahidhara RS, Queiroz De Oliveira PE, Kohout J et al (2005) Altered trafficking of Fas and subsequent resistance to Fas-mediated apoptosis occurs by a wild-type p53 independent mechanism in esophageal adenocarcinoma. J Surg Res 123(2):302–311

    Article  PubMed  CAS  Google Scholar 

  33. Korotayev K, Ginsberg D (2008) Many pathways to apoptosis: E2F1 regulates splicing of apoptotic genes. Cell Death Differ 15(2):1813–1814

    Article  PubMed  CAS  Google Scholar 

  34. Gartel AL, Tyner AL (2002) The role of the cyclin-dependent kinase inhibitor p21 in apoptosis. Mol Cancer Ther 1(8):639–649

    PubMed  CAS  Google Scholar 

  35. Hiromura K, Pippin JW, Fero ML (1999) Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). J Clin Invest 103(5):597–604

    Article  PubMed  CAS  Google Scholar 

  36. Pucci B, Kasten M, Giordano A (2000) Cell cycle and apoptosis. Neoplasia 2(4):291–299

    Article  PubMed  CAS  Google Scholar 

  37. Collins NL, Reginato MJ, Paulus JK (2005) G1/S cell cycle arrest provides anoikis resistance through Erk-mediated Bim suppression. Mol Cell Biol 25(12):5282–5291

    Article  PubMed  CAS  Google Scholar 

  38. Lin Y, Bai L, Chen W, Xu S (2010) The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy. Expert Opin Ther Targets 14(1):45–55

    Article  PubMed  CAS  Google Scholar 

  39. Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5(10):749–759

    Article  PubMed  CAS  Google Scholar 

  40. Vachon PH (2011) Integrin signaling, cell survival, and anoikis: distinctions, differences, and differentiation. J Signal Transduct 2011:738137

    PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Foundation of Natural Sciences, China (No. 81101533, No. 81071727 and No. 81170356) and China Postdoctoral Science Foundation (No. 20100481468 and No. 201104755).

Conflict of interest

The authors state no conflicts of interest

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China

    Ya-Fei Zhang, An-Ran Zhang, Mu-Han Lv, Yu-Yun Wu, Su-Min Wang, Rong-Quan Wang & Dian-Chun Fang

  2. Department of Oncology, Wuhan General Hospital of Guangzhou Command, People’s Liberation Army, Wuhan, 430070, China

    Ya-Fei Zhang, Bi-Cheng Zhang, Zhi-Guo Rao & Jian-Fei Gao

Authors
  1. Ya-Fei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. An-Ran Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bi-Cheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhi-Guo Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian-Fei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mu-Han Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu-Yun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Su-Min Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rong-Quan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dian-Chun Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dian-Chun Fang.

Additional information

Ya-Fei Zhang and An-Ran Zhang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, YF., Zhang, AR., Zhang, BC. et al. MiR-26a regulates cell cycle and anoikis of human esophageal adenocarcinoma cells through Rb1-E2F1 signaling pathway. Mol Biol Rep 40, 1711–1720 (2013). https://doi.org/10.1007/s11033-012-2222-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2222-7

Keywords

Search

Navigation