Skip to main content

Advertisement

SpringerLink
Log in

MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

MicroRNA (miRNA) is a small noncoding RNA molecule, 19–25 nucleotides in length, which regulates several pathways including cell development, cell proliferation, carcinogenesis, apoptosis, etc. In this study, the over-expression of microRNA-205 (miR-205) increased the number of apoptotic cells by at least 4 times compared to the control. In addition, over-expressed miRNA in KB oral cancer cells triggered apoptosis via the caspase cascade, including the cleavage of caspase-9, caspase-7, caspase-3, and PARP. Flow cytometry showed that apoptotic cell death was increased significantly by 35.33 % in KB oral cancer cells with over-expressed miR-205 compared to the control. The microarray data showed that axis inhibitor protein 2 (Axin2) was down-regulated in KB oral cancer cells transfected with miR-205. In addition, Axin2 was down-regulated by approximately 50 % by over-expressed miR-205 at both the mRNA and protein levels. Interestingly, Axin2 was up-regulated in KB oral cancer compared to human normal oral keratinocytes. Furthermore, the cell cytotoxicity and apoptotic population of KB oral cancer cells were increased significantly after Axin2 siRNA transfection. These results suggest that Axin2 is might be as potential oncogene in KB oral cancer cells. The luciferase assay showed that over-expressed miR-205 in KB oral cancer cells suppressed AXIN2 expression through an interaction with its own binding site at AXIN2 3′UTR (64–92). These results suggest that miR-205 is a novel anti-oncogenic miRNA in KB oral cancer cells, and may have potential applications in oral cancer therapy.

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

Similar content being viewed by others

References

  1. Cho HJ, Liu G, Jin SM, Parisiadou L, Xie C, Yu J, Sun L, Ma B, Ding J, Vancraenenbroeck R, Lobbestael E, Baekelandt V, Taymans JM, He P, Troncoso JC, Shen Y, Cai H (2013) MicroRNA-205 regulates the expression of Parkinson’s disease-related leucine-rich repeat kinase 2 protein. Hum Mol Genet 22:608–620. doi:10.1093/hmg/dds470

    Article  CAS  PubMed  Google Scholar 

  2. Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, Stein GS (2011) A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci USA 108:9863–9868. doi:10.1073/pnas.1018493108

    Article  CAS  PubMed  Google Scholar 

  3. Liu J, Mao Q, Liu Y, Hao X, Zhang S, Zhang J (2013) Analysis of miR-205 and miR-155 expression in the blood of breast cancer patients. Chin J Cancer Res 25:46–54. doi:10.3978/j.issn.1000-9604.2012.11.04

    PubMed Central  PubMed  Google Scholar 

  4. Kim JS, Yu SK, Lee MH, Park MG, Park E, Kim SG, Lee SY, Kim CS, Kim HJ, Chun HS, Chun SW, Kim do K (2013) MicroRNA-205 directly regulates the tumor suppressor, interleukin-24, in human KB oral cancer cells. Mol Cells 35:17–24. doi:10.1007/s10059-013-2154-7

    Article  CAS  PubMed  Google Scholar 

  5. Majid S, Dar AA, Saini S, Yamamura S, Hirata H, Tanaka Y, Deng G, Dahiya R (2010) MicroRNA-205-directed transcriptional activation of tumor suppressor genes in prostate cancer. Cancer 116:5637–5649. doi:10.1002/cncr.25488

    Article  CAS  PubMed  Google Scholar 

  6. Tucci P, Agostini M, Grespi F, Markert EK, Terrinoni A, Vousden KH, Muller PA, Dotsch V, Kehrloesser S, Sayan BS, Giaccone G, Lowe SW, Takahashi N, Vandenabeele P, Knight RA, Levine AJ, Melino G (2012) Loss of p63 and its microRNA-205 target results in enhanced cell migration and metastasis in prostate cancer. Proc Natl Acad Sci USA 109:15312–15317. doi:10.1073/pnas.1110977109

    Article  CAS  PubMed  Google Scholar 

  7. Liu S, Tetzlaff MT, Liu A, Liegl-Atzwanger B, Guo J, Xu X (2012) Loss of microRNA-205 expression is associated with melanoma progression. Lab Invest 92:1084–1096. doi:10.1038/labinvest.2012.62

    Article  CAS  PubMed  Google Scholar 

  8. Yue X, Wang P, Xu J, Zhu Y, Sun G, Pang Q, Tao R (2012) MicroRNA-205 functions as a tumor suppressor in human glioblastoma cells by targeting VEGF-A. Oncol Rep 27:1200–1206. doi:10.3892/or.2011.1588

    CAS  PubMed  Google Scholar 

  9. Song H, Bu G (2009) MicroRNA-205 inhibits tumor cell migration through down-regulating the expression of the LDL receptor-related protein 1. Biochem Biophys Res Commun 388:400–405. doi:10.1016/j.bbrc.2009.08.020

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Iorio MV, Casalini P, Piovan C, Di Leva G, Merlo A, Triulzi T, Menard S, Croce CM, Tagliabue E (2009) microRNA-205 regulates HER3 in human breast cancer. Cancer Res 69:2195–2200. doi:10.1158/0008-5472.CAN-08-2920

    Article  CAS  PubMed  Google Scholar 

  11. Majid S, Saini S, Dar AA, Hirata H, Shahryari V, Tanaka Y, Yamamura S, Ueno K, Zaman MS, Singh K, Chang I, Deng G, Dahiya R (2011) MicroRNA-205 inhibits Src-mediated oncogenic pathways in renal cancer. Cancer Res 71:2611–2621. doi:10.1158/0008-5472.CAN-10-3666

    Article  CAS  PubMed  Google Scholar 

  12. Verdoodt B, Neid M, Vogt M, Kuhn V, Liffers ST, Palisaar RJ, Noldus J, Tannapfel A, Mirmohammadsadegh A (2013) MicroRNA-205, a novel regulator of the anti-apoptotic protein Bcl2, is downregulated in prostate cancer. Int J Oncol 43:307–314. doi:10.3892/ijo.2013.1915

    CAS  PubMed  Google Scholar 

  13. Noguchi S, Iwasaki J, Kumazaki M, Mori T, Maruo K, Sakai H, Yamada N, Shimada K, Naoe T, Kitade Y, Akao Y (2013) Chemically modified synthetic microRNA-205 inhibits the growth of melanoma cells in vitro and in vivo. Mol Ther. doi:10.1038/mt.2013.70

    PubMed  Google Scholar 

  14. Gandellini P, Profumo V, Casamichele A, Fenderico N, Borrelli S, Petrovich G, Santilli G, Callari M, Colecchia M, Pozzi S, De Cesare M, Folini M, Valdagni R, Mantovani R, Zaffaroni N (2012) miR-205 regulates basement membrane deposition in human prostate: implications for cancer development. Cell Death Differ 19:1750–1760. doi:10.1038/cdd.2012.56

    Article  CAS  PubMed  Google Scholar 

  15. Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F (2002) Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 22:1172–1183

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Lustig B, Jerchow B, Sachs M, Weiler S, Pietsch T, Karsten U, van de Wetering M, Clevers H, Schlag PM, Birchmeier W, Behrens J (2002) Negative feedback loop of Wnt signaling through upregulation of conductin/axin2 in colorectal and liver tumors. Mol Cell Biol 22:1184–1193

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Cheng CW, Smith SK, Charnock-Jones DS (2003) Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and alters cell morphology. Exp Cell Res 291:415–425

    Article  CAS  PubMed  Google Scholar 

  18. Masckauchan TN, Shawber CJ, Funahashi Y, Li CM, Kitajewski J (2005) Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells. Angiogenesis 8:43–51. doi:10.1007/s10456-005-5612-9

    Article  CAS  PubMed  Google Scholar 

  19. Ille F, Atanasoski S, Falk S, Ittner LM, Marki D, Buchmann-Moller S, Wurdak H, Suter U, Taketo MM, Sommer L (2007) Wnt/BMP signal integration regulates the balance between proliferation and differentiation of neuroepithelial cells in the dorsal spinal cord. Dev Biol 304:394–408. doi:10.1016/j.ydbio.2006.12.045

    Article  CAS  PubMed  Google Scholar 

  20. Espada J, Calvo MB, Diaz-Prado S, Medina V (2009) Wnt signalling and cancer stem cells. Clin Transl Oncol 11:411–427

    Article  CAS  PubMed  Google Scholar 

  21. Gaujoux S, Hantel C, Launay P, Bonnet S, Perlemoine K, Lefevre L, Guillaud-Bataille M, Beuschlein F, Tissier F, Bertherat J, Rizk-Rabin M, Ragazzon B (2013) Silencing mutated beta-catenin inhibits cell proliferation and stimulates apoptosis in the adrenocortical cancer cell line H295R. PLoS One 8:e55743. doi:10.1371/journal.pone.0055743

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Behrens J (2005) The role of the Wnt signalling pathway in colorectal tumorigenesis. Biochem Soc Trans 33:672–675. doi:10.1042/BST0330672

    Article  CAS  PubMed  Google Scholar 

  23. Pan KF, Liu WG, Zhang L, You WC, Lu YY (2008) Mutations in components of the Wnt signaling pathway in gastric cancer. World J Gastroenterol 14:1570–1574

    Article  CAS  PubMed  Google Scholar 

  24. Kim MS, Kim SS, Ahn CH, Yoo NJ, Lee SH (2009) Frameshift mutations of Wnt pathway genes AXIN2 and TCF7L2 in gastric carcinomas with high microsatellite instability. Hum Pathol 40:58–64. doi:10.1016/j.humpath.2008.06.006

    Article  CAS  PubMed  Google Scholar 

  25. Kim NH, Cha YH, Kang SE, Lee Y, Lee I, Cha SY, Ryu JK, Na JM, Park C, Yoon HG, Park GJ, Yook JI, Kim HS (2013) p53 regulates nuclear GSK-3 levels through miR-34-mediated Axin2 suppression in colorectal cancer cells. Cell Cycle 12:1578–1587. doi:10.4161/cc.24739

    Article  CAS  PubMed  Google Scholar 

  26. Wu ZQ, Brabletz T, Fearon E, Willis AL, Hu CY, Li XY, Weiss SJ (2012) Canonical Wnt suppressor, Axin2, promotes colon carcinoma oncogenic activity. Proc Natl Acad Sci USA 109:11312–11317. doi:10.1073/pnas.1203015109

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2012R1A1A2001175).

Conflict of interest

We declare that there is no conflict of interest. No author has any financial interest or conflict of interest involved with this study.

Author information

Authors and Affiliations

  1. Oral Biology Research Institute, School of Dentistry, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea

    Jae-Sung Kim, Sun-Young Park, Seul Ah Lee, Min-Gyeong Park, Sun-Kyoung Yu, Myoung-Hwa Lee, Mi-Ra Park, Su-Gwan Kim, Ji-Su Oh, Sook-Young Lee, Chun Sung Kim, Heung-Joong Kim, Jin-Soo Kim, Sung-Min Moon & Do Kyung Kim

  2. Department of Biotechnology, Chosun University, 375 Seosuk-dong, Dong-gu, Gwangju, 501-759, Republic of Korea

    Hong Sung Chun

Authors
  1. Jae-Sung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sun-Young Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seul Ah Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min-Gyeong Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sun-Kyoung Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Myoung-Hwa Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mi-Ra Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Su-Gwan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ji-Su Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Sook-Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Chun Sung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Heung-Joong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hong Sung Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Jin-Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Sung-Min Moon
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Do Kyung Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Do Kyung Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, JS., Park, SY., Lee, S.A. et al. MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell. Mol Cell Biochem 387, 71–79 (2014). https://doi.org/10.1007/s11010-013-1872-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1872-7

Keywords

Search

Navigation