Skip to main content

Advertisement

SpringerLink
Log in

miR-185 is an independent prognosis factor and suppresses tumor metastasis in gastric cancer

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

Abstract

miR-185 has been identified as an important factor in several cancers such as breast cancer, ovarial cancer, and prostate cancer. However, its effect and prognostic value in gastric cancer are still poorly known. In this study, we found that the expression levels of miR-185 were strongly downregulated in gastric cancer and associated with clinical stage and the presence of lymph node metastases. Moreover, miR-185 might independently predict OS and RFS in gastric cancer. We further found that upregulation of miR-185 inhibited the proliferation and metastasis of gastric cancer cells in vitro and in vivo. Taken together, our findings demonstrate that the miR-185 is important for gastric cancer initiation and progression and holds promise as a prognostic biomarker to predict survival and relapse in gastric cancer. It is also a potential therapeutic tool to improve clinical outcomes in the above disease.

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

Similar content being viewed by others

References

  1. Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ (2009) Gastric cancer. Lancet 374:477–490. doi:10.1016/S0140-6736(09)60617-6

    Article  PubMed  Google Scholar 

  2. Kamangar F, Dores GM, Anderson WF (2006) Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol 24:2137–2150. doi:10.1200/JCO.2005.05.2308

    Article  PubMed  Google Scholar 

  3. Schickel R, Boyerinas B, Park SM, Peter ME (2008) MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene 27:5959–5974. doi:10.1038/onc.2008.274

    Article  CAS  PubMed  Google Scholar 

  4. Ventura A, Jacks T (2009) MicroRNAs and cancer: short RNAs go a long way. Cell 136:586–591. doi:10.1016/j.cell.2009.02.005

    Article  CAS  PubMed  Google Scholar 

  5. Slack FJ, Weidhaas JB (2008) MicroRNA in cancer prognosis. N Engl J Med 359:2720–2722. doi:10.1056/NEJMe0808667

    Article  CAS  PubMed  Google Scholar 

  6. Hurst DR, Edmonds MD, Welch DR (2009) Metastamir: the field of metastasis-regulatory microRNA is spreading. Cancer Res 69:7495–7498. doi:10.1158/0008-5472.CAN-09-2111

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bartels CL, Tsongalis GJ (2009) MicroRNAs: novel biomarkers for human cancer. Clin Chem 55:623–631. doi:10.1373/clinchem.2008.112805

    Article  CAS  PubMed  Google Scholar 

  8. Akcakaya P, Ekelund S, Kolosenko I, Caramuta S, Ozata DM, Xie H, Lindforss U, Olivecrona H, Lui WO (2011) miR-185 and miR-133b deregulation is associated with overall survival and metastasis in colorectal cancer. Int J Oncol 39:311–318. doi:10.3892/ijo.2011.1043

    PubMed  Google Scholar 

  9. Liu M, Lang N, Chen X, Tang Q, Liu S, Huang J, Zheng Y, Bi F (2011) miR-185 targets RhoA and Cdc42 expression and inhibits the proliferation potential of human colorectal cells. Cancer Lett 301:151–160. doi:10.1016/j.canlet.2010.11.009

    Article  CAS  PubMed  Google Scholar 

  10. Zhi Q, Zhu J, Guo X, He S, Xue X, Zhou J, Hu B, Li H, Chen S, Zhao H, Kuang Y (2013) Metastasis-related miR-185 is a potential prognostic biomarker for hepatocellular carcinoma in early stage. Biomed Pharmacother 67:393–398. doi:10.1016/j.biopha.2013.03.022

    Article  CAS  PubMed  Google Scholar 

  11. Xiang Y, Ma N, Wang D, Zhang Y, Zhou J, Wu G, Zhao R, Huang H, Wang X, Qiao Y, Li F, Han D, Wang L, Zhang G, Gao X (2013) MiR-152 and miR-185 co-contribute to ovarian cancer cells cisplatin sensitivity by targeting DNMT1 directly: a novel epigenetic therapy independent of decitabine. Oncogene. doi:10.1038/onc.2012.575

    Google Scholar 

  12. Imam JS, Buddavarapu K, Lee-Chang JS, Ganapathy S, Camosy C, Chen Y, Rao MK (2010) MicroRNA-185 suppresses tumor growth and progression by targeting the Six1 oncogene in human cancers. Oncogene 29:4971–4979. doi:10.1038/onc.2010.233

    Article  CAS  PubMed  Google Scholar 

  13. Qu F, Cui X, Hong Y, Wang J, Li Y, Chen L, Liu Y, Gao Y, Xu D, Wang Q (2013) MicroRNA-185 suppresses proliferation, invasion, migration, and tumorigenicity of human prostate cancer cells through targeting androgen receptor. Mol Cell Biochem 377:121–130. doi:10.1007/s11010-013-1576-z

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Z, Tang H, Wang Z, Zhang B, Liu W, Lu H, Xiao L, Liu X, Wang R, Li X, Wu M, Li G (2011) MiR-185 targets the DNA methyltransferases 1 and regulates global DNA methylation in human glioma. Mol Cancer 10:124. doi:10.1186/1476-4598-10-124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Tang H, Wang Z, Liu X, Liu Q, Xu G, Li G, Wu M (2012) LRRC4 inhibits glioma cell growth and invasion through a miR-185-dependent pathway. Curr Cancer Drug Targets 12:1032–1042

    Article  CAS  PubMed  Google Scholar 

  16. Tang H, Bian Y, Tu C, Wang Z, Yu Z, Liu Q, Xu G, Wu M, Li G (2013) The miR-183/96/182 cluster regulates oxidative apoptosis and sensitizes cells to chemotherapy in gliomas. Curr Cancer Drug Targets 13:221–231

    Article  CAS  PubMed  Google Scholar 

  17. Deng M, Ye Q, Qin Z, Zheng Y, He W, Tang H, Zhou Y, Xiong W, Zhou M, Li X, Yan Q, Ma J, Li G (2013) miR-214 promotes tumorigenesis by targeting lactotransferrin in nasopharyngeal carcinoma. Tumour Biol 34:1793–1800. doi:10.1007/s13277-013-0718-y

    Article  CAS  PubMed  Google Scholar 

  18. Li X, Zhang Y, Zhang Y, Ding J, Wu K, Fan D (2010) Survival prediction of gastric cancer by a seven-microRNA signature. Gut 59:579–585. doi:10.1136/gut.2008.175497

    Article  CAS  PubMed  Google Scholar 

  19. Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, Yoshida K, Sasaki H, Nomura S, Seto Y, Kaminishi M, Calin GA, Croce CM (2010) Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol 11:136–146. doi:10.1016/S1470-2045(09)70343-2

    Article  CAS  PubMed  Google Scholar 

  20. Tie J, Pan Y, Zhao L, Wu K, Liu J, Sun S, Guo X, Wang B, Gang Y, Zhang Y, Li Q, Qiao T, Zhao Q, Nie Y, Fan D (2010) MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet 6:e1000879. doi:10.1371/journal.pgen.1000879

    Article  PubMed Central  PubMed  Google Scholar 

  21. Coburn NG (2009) Lymph nodes and gastric cancer. J Surg Oncol 99:199–206. doi:10.1002/jso.21224

    Article  PubMed  Google Scholar 

  22. Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, Liu L, Jia D, Tian Q, Wu J, Ye Y, Wang Q, Long Z, Zhou Y, Du C, He X, Shi Y (2011) MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res 17:7574–7583. doi:10.1158/1078-0432.CCR-11-1714

    Article  CAS  PubMed  Google Scholar 

  23. Oh HK, Tan AL, Das K, Ooi CH, Deng NT, Tan IB, Beillard E, Lee J, Ramnarayanan K, Rha SY, Palanisamy N, Voorhoeve PM, Tan P (2011) Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer. Clin Cancer Res 17:2657–2667. doi:10.1158/1078-0432.CCR-10-3152

    Article  CAS  PubMed  Google Scholar 

  24. Nishida N, Mimori K, Fabbri M, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M (2011) MicroRNA-125a-5p is an independent prognostic factor in gastric cancer and inhibits the proliferation of human gastric cancer cells in combination with trastuzumab. Clin Cancer Res 17:2725–2733. doi:10.1158/1078-0432.CCR-10-2132

    Article  CAS  PubMed  Google Scholar 

  25. Lo SS, Hung PS, Chen JH, Tu HF, Fang WL, Chen CY, Chen WT, Gong NR, Wu CW (2012) Overexpression of miR-370 and downregulation of its novel target TGFbeta-RII contribute to the progression of gastric carcinoma. Oncogene 31:226–237. doi:10.1038/onc.2011.226

    Article  CAS  PubMed  Google Scholar 

  26. Kogo R, Mimori K, Tanaka F, Komune S, Mori M (2011) Clinical significance of miR-146a in gastric cancer cases. Clin Cancer Res 17:4277–4284. doi:10.1158/1078-0432.CCR-10-2866

    Article  CAS  PubMed  Google Scholar 

  27. Li X, Zhang Y, Shi Y, Dong G, Liang J, Han Y, Wang X, Zhao Q, Ding J, Wu K, Fan D (2011) MicroRNA-107, an oncogene microRNA that regulates tumour invasion and metastasis by targeting DICER1 in gastric cancer. J Cell Mol Med 15:1887–1895. doi:10.1111/j.1582-4934.2010.01194.x

    Article  CAS  PubMed  Google Scholar 

  28. Sun T, Wang C, Xing J, Wu D (2011) miR-429 modulates the expression of c-myc in human gastric carcinoma cells. Eur J Cancer 47:2552–2559. doi:10.1016/j.ejca.2011.05.021

    Article  CAS  PubMed  Google Scholar 

  29. Takahashi Y, Forrest AR, Maeno E, Hashimoto T, Daub CO, Yasuda J (2009) MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines. PLoS ONE 4:e6677. doi:10.1371/journal.pone.0006677

    Article  PubMed Central  PubMed  Google Scholar 

  30. Liao JM, Lu H (2011) Autoregulatory suppression of c-Myc by miR-185-3p. J Biol Chem 286:33901–33909. doi:10.1074/jbc.M111.262030

    Article  CAS  PubMed  Google Scholar 

  31. Tang H, Deng M, Tang Y, Xie X, Guo J, Kong Y, Ye F, Su Q, Xie X (2013) miR-200b and miR-200c as prognostic factors and mediators of gastric cancer cell progression. Clin Cancer Res. doi:10.1158/1078-0432.CCR-13-1326

    PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the Nature Scientific Foundation of China (31100935).

Conflict of interest

No potential conflicts of interest are disclosed.

Author information

Authors and Affiliations

  1. Center for Gastric Cancer Research of Human Province, The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang, 421001, People’s Republic of China

    Zhiqin Tan, Hao Jiang, Youhua Wu, Liming Xie, Wenxiang Dai & Sanyuan Tang

  2. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, 651 East Dongfeng Road, Guangzhou, 510060, People’s Republic of China

    Hailin Tang

  3. Department of Gynaecology and Obstetrics, The 169th Hospital of PLA, 369 South Dongfeng Road, Hengyang, 421002, People’s Republic of China

    Zhiqin Tan

Authors
  1. Zhiqin Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hao Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Youhua Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Liming Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wenxiang Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hailin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sanyuan Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Hailin Tang or Sanyuan Tang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, Z., Jiang, H., Wu, Y. et al. miR-185 is an independent prognosis factor and suppresses tumor metastasis in gastric cancer. Mol Cell Biochem 386, 223–231 (2014). https://doi.org/10.1007/s11010-013-1860-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1860-y

Keywords

Search

Navigation