Expression of microRNA-218 and its Clinicopathological and Prognostic Significance in Human Glioma Cases

  • Cheng, Mao-Wei (College of Command Information System, PLA University of Science and Technology) ;
  • Wang, Ling-Ling (Department of Medical Education, Jinling Hospital, School of Medicine, Nanjing University) ;
  • Hu, Gu-Yu (College of Command Information System, PLA University of Science and Technology)
  • Published : 2015.03.18


Background: MicroRNAs are a class of noncoding RNAs which regulate multiple cellular processes during tumor development. The purpose of this report is to investigate the clinicopathological and prognostic significance of miR-218 in human gliomas. Materials and Methods: Quantitative RT-PCR (qRT-PCR) was conducted to detect the expression of miR-218 in primary normal human astrocytes, three glioma cell lines and 98 paired glioma and adjacent normal brain tissues.Associations of miR-218 with clinicopathological variables of glioma patients were statistically analyzed. Finally, a survival analysis was performed using the Kaplan-Meier method and Cox's proportional hazards model. Results: The expression level of miR-218 in primary normal human astrocytes was significantly higher than that in glioma cell lines (p<0.01). Also, the expression level of miR-218 in glioma tissues was significantly downregulated in comparison with that in the adjacent normal brain tissues (p<0.001). Statistical analyses demonstrated that low miR-218 expression was closely associated with advanced WHO grade (p=0.002) and low Karnofsky performance score (p=0.010) of glioma patients. Kaplan-Meier analysis with the log-rank test showed that patients with low-miR-218 expression had poorer disease-free survival and overall survival (p=0.0045 and 0.0124, respectively). Multivariate analysis revealed that miR-218 expression was independently associated with the disease-free survival (p=0.009) and overall survival (p=0.004) of glioma patients. Conclusions: Our results indicate that miR-218 is downregulated in gliomas and that its status might be a potential valuable biomarker for glioma patients.


Glioma;microRNA-218;disease-free survival;overall survival


  1. Asuthkar S, Velpula KK, Chetty C, et al (2012). Epigenetic regulation of miRNA-211 by MMP-9 governs glioma cell apoptosis, chemosensitivity and radiosensitivity. Oncotarget, 3, 1439-54.
  2. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116, 281-97.
  3. Chen W, Yang Y, Chen B, et al (2014). MiR-136 targets E2F1 to reverse cisplatin chemosensitivity in glioma cells. J Neurooncol, 120, 43-53.
  4. Costa FF (2005). Non-coding RNAs: new players in eukaryotic biology. Gene, 357, 83-94.
  5. Friedman JM, Jones PA (2009). MicroRNAs: critical mediators of differentiation, development and disease. Swiss Med Wkly, 139, 466-72.
  6. Gao X, Jin W (2014). The emerging role of tumor-suppressive microRNA-218 in targeting glioblastoma stemness. Cancer Lett, 353, 25-31.
  7. He H, Hao SJ, Yao L, et al (2014). MicroRNA-218 inhibits cell invasion and migration of pancreatic cancer via regulating ROBO1. Cancer Biol Ther, 15, 1333-9.
  8. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 6, 69-90.
  9. Louis DN, Ohgaki H, Wiestler OD, et al (2007). The 2007 WHO classification of tumours ofthe central nervous system. Acta Neuropathol, 114, 97-109.
  10. Mathew LK, Skuli N, Mucaj V, et al (2014). miR-218 opposes a critical RTK-HIF pathway in mesenchymal glioblastoma. Proc Natl Acad Sci USA, 111, 291-6.
  11. Nishikawa R, Goto Y, Sakamoto S, et al (2014). Tumorsuppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer. Cancer Sci, 105, 802-11.
  12. Sevignani C, Calin GA, Siracusa LD, et al (2006). Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome, 17, 189-202.
  13. Shenouda SK, Alahari SK (2009). MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev, 28, 369-78.
  14. Sun J, Shi H, Lai N, et al (2014). Overexpression of microRNA-155 predicts poor prognosis in glioma patients. Med Oncol, 31, 911.
  15. Taylor LP (2010). Diagnosis, treatment, and prognosis of glioma: five new things. Neurology, 75, 28-32.
  16. Tu K, Li C, Zheng X, et al (2014). Prognostic significance of miR-218 in human hepatocellular carcinoma and its role in cell growth. Oncol Rep, 32, 1571-7.
  17. Tu Y, Gao X, Li G, et al (2013). MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res, 73, 6046-55.
  18. Tufekci KU, Meuwissen RL, Genc S (2014). The role of microRNAs in biological processes. Methods Mol Biol, 1107, 15-31.
  19. Venkataraman S, Birks DK, Balakrishnan I, et al (2013). MicroRNA 218 acts as a tumor suppressor by targeting multiple cancer phenotype-associated genes in medulloblastoma. J Biol Chem, 288, 1918-28.
  20. Wang J, Sai K, Chen FR, et al (2013). miR-181b modulates glioma cell sensitivity to temozolomide by targeting MEK1. Cancer Chemother Pharmacol, 72, 147-58.
  21. Wang S, Jiao B, Geng S, et al (2014). Combined aberrant expression of microRNA-214 and UBC9 is an independent unfavorable prognostic factor for patients with gliomas. Med Oncol, 31, 767.
  22. Wu L, Li G, Feng D, et al (2013). MicroRNA-21 expression is associated with overall survival in patients with glioma. Diagn Pathol, 8, 200.
  23. Yamamoto N, Kinoshita T, Nohata N, et al (2013). Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion by targeting focal adhesion pathways in cervical squamous cell carcinoma. Int J Oncol, 42, 1523-32.
  24. Yamasaki T, Seki N, Yoshino H, et al (2013). MicroRNA-218 inhibits cell migration and invasion in renal cell carcinoma through targeting caveolin-2 involved in focal adhesion pathway. J Urol, 190, 1059-68.
  25. Yang L, Li Q, Wang Q, et al (2012). Silencing of miRNA-218 promotes migration and invasion of breast cancer via Slit2- Robo1 pathway. Biomed Pharmacother, 66, 535-40.
  26. Yang YP, Chien Y, Chiou GY, et al (2012). Inhibition of cancer stem cell-like properties and reduced chemoradioresistance of glioblastoma using microRNA145 with cationic polyurethane-short branch PEI. Biomaterials, 33, 1462-76.
  27. Zhang Y, Dutta A, Abounader R (2012). The role of microRNAs in glioma initiation and progression. Front Biosci, 17, 700-12.
  28. Zhu Z, Xu Y, Du J, et al (2014). Expression of microRNA-218 in human pancreatic ductal adenocarcinoma and its correlation with tumor progression and patient survival. J Surg Oncol, 109, 89-94.

Cited by

  1. Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis vol.39, pp.8, 2017,
  2. Prognostic significance of low microRNA-218 expression in patients with different types of cancer vol.95, pp.37, 2016,