Skip to main content
Log in

Increased expression of microRNA-9 predicts an unfavorable prognosis in human glioma

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

Abstract

microRNA-9 (miR-9) has been found to be upregulated along with tumor progression of gliomas by microarray-based expression profiling, and also be strongly linked to glioblastoma subtypes. However, its prognostic value in glioma is still elusive. miR-9 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay. miR-9 expression in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). The increased expression of miR-9 was more frequently observed in glioma tissues with high WHO grade than those with low WHO grade tissues (P = 0.001). The expression levels of miR-9 in glioma tissues with low Karnofsky performance score (KPS) were also significantly higher than those with high KPS (P = 0.008). Moreover, the overall survival of glioma patients with high miR-9 expression was obviously lower than that with low miR-9 expression (P < 0.001). Multivariate analysis further showed that high miR-9 expression was an independent prognostic factor for overall survival in glioma patients (P = 0.01). More importantly, the subgroup analyses indicated that the overall survival of glioma patients with high WHO grade (III–IV) was significantly worse for high miR-9 expression group than for low miR-9 expression group (P < 0.001), but no significant difference was found for patients with low WHO grade (I–II). These findings suggest for the first time that the increased expression of miR-9 may play an important role in tumor progression in human gliomas. miR-9 might be a useful marker for predicting the clinical outcome of glioma patients, especially for advanced subtypes.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Rousseau A, Mokhtari K, Duyckaerts C (2008) The 2007 WHO classification of tumors of the central nervous system—what has changed? Curr Opin Neurol 21:720–727

    Article  PubMed  Google Scholar 

  2. Chu SH, Ma YB, Feng DF, Zhang H, Zhu ZA, Li ZQ, Jiang PC (2012) Correlation of low SLC22A18 expression with poor prognosis in patients with glioma. J Clin Neurosci 19:95–98

    Article  PubMed  CAS  Google Scholar 

  3. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    Article  PubMed  Google Scholar 

  4. Zhang X, Yang H, Gong B, Jiang C, Yang L (2012) Combined gene expression and protein interaction analysis of dynamic modularity in glioma prognosis. J Neurooncol 107:281–288

    Article  PubMed  CAS  Google Scholar 

  5. Curran WJ Jr, Scott CB (1996) Radiosurgery for glioma patients: hope or hype? Int J Radiat Oncol Biol Phys 36:1279–1280

    Article  PubMed  Google Scholar 

  6. Esteller M (2011) Non coding RNAs in human disease. Nat Rev Genet 2011:861–874

    Article  Google Scholar 

  7. van Kouwenhove M, Kedde M, Agami R (2011) microRNA regulation by RNA binding proteins and its implications for cancer. Nat Rev Cancer 11:644–656

    Article  PubMed  Google Scholar 

  8. Saal S, Harvey SJ (2009) microRNAs and the kidney: coming of age. Curr Opin Nephrol Hypertens 18:317–323

    Article  PubMed  CAS  Google Scholar 

  9. Rao SA, Santosh V, Somasundaram K (2010) Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. Mod Pathol 23:1404–1417

    Article  PubMed  CAS  Google Scholar 

  10. Tang H, Yao L, Tao X, Yu Y, Chen M, Zhang R, Xu C (2013) miR-9 functions as a tumor suppressor in ovarian serous carcinoma by targeting TLN1. Int J Mol Med. doi:10.3892/ijmm.2013.1400

  11. Sun Z, Han Q, Zhou N, Wang S, Lu S, Bai C, Zhao RC (2013) microRNA-9 enhances migration and invasion through KLF17 in hepatocellular carcinoma. Mol Oncol 7:884–894

    Google Scholar 

  12. Wang J, Zhao H, Tang D, Wu J, Yao G, Zhang Q (2013) Overexpressions of microRNA-9 and microRNA-200c in human breast cancers are associated with lymph node metastasis. Cancer Biother Radiopharm. (in press)

  13. Saito Y, Saito H (2012) microRNAs in cancers and neurodegenerative disorders. Front Genet 3:194

    PubMed  CAS  Google Scholar 

  14. Nass D, Rosenwald S, Meiri E, Gilad S, Tabibian-Keissar H, Schlosberg A, Kuker H, Sion-Vardy N, Tobar A, Kharenko O, Sitbon E, Lithwick Yanai G, Elyakim E, Cholakh H, Gibori H, Spector Y, Bentwich Z, Barshack I, Rosenfeld N (2009) MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol 19:375–383

    Article  PubMed  CAS  Google Scholar 

  15. Krell J, Frampton AE, Jacob J, Pellegrino L, Roca-Alonso L, Zeloof D, Alifrangis C, Lewis JS, Jiao LR, Stebbing J, Castellano L (2012) The clinico-pathologic role of microRNAs miR-9 and miR-151-5p in breast cancer metastasis. Mol Diagn Ther 16:167–172

    Article  PubMed  CAS  Google Scholar 

  16. Zhu L, Chen H, Zhou D, Li D, Bai R, Zheng S, Ge W (2012) microRNA-9 up-regulation is involved in colorectal cancer metastasis via promoting cell motility. Med Oncol 29:1037–1043

    Article  PubMed  CAS  Google Scholar 

  17. Leucci E, Zriwil A, Gregersen LH, Jensen KT, Obad S, Bellan C, Leoncini L, Kauppinen S, Lund AH (2012) Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo. Oncogene 31:5081–5089

    Article  PubMed  CAS  Google Scholar 

  18. Zheng L, Qi T, Yang D, Qi M, Li D, Xiang X, Huang K, Tong Q (2013) microRNA-9 suppresses the proliferation, invasion and metastasis of gastric cancer cells through targeting cyclin D1 and Ets1. PLoS One 8:e55719

    Article  PubMed  CAS  Google Scholar 

  19. Liu N, Sun Q, Chen J, Li J, Zeng Y, Zhai S, Li P, Wang B, Wang X (2012) microRNA-9 suppresses uveal melanoma cell migration and invasion through the NF-κB1 pathway. Oncol Rep 28:961–968

    PubMed  Google Scholar 

  20. Guo R, Wu Q, Liu F, Wang Y (2011) Description of the CD133+ subpopulation of the human ovarian cancer cell line OVCAR3. Oncol Rep 25:141–146

    PubMed  CAS  Google Scholar 

  21. Gao F, Zhao ZL, Zhao WT, Fan QR, Wang SC, Li J, Zhang YQ, Shi JW, Lin XL, Yang S, Xie RY, Liu W, Zhang TT, Sun YL, Xu K, Yao KT, Xiao D (2013) miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells. Biochem Biophys Res Commun 431:610–616

    Article  PubMed  CAS  Google Scholar 

  22. Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stühler K, Meyer HE, Reifenberger G (2010) Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol 20:539–550

    Article  PubMed  CAS  Google Scholar 

  23. Kim TM, Huang W, Park R, Park PJ, Johnson MD (2011) A developmental taxonomy of glioblastoma defined and maintained by microRNAs. Cancer Res 71:3387–3399

    Article  PubMed  CAS  Google Scholar 

  24. Ben-Hamo R, Efroni S (2011) Gene expression and network-based analysis reveals a novel role for hsa-miR-9 and drug control over the p38 network in glioblastoma multiforme progression. Genome Med 3:77

    Article  PubMed  CAS  Google Scholar 

  25. Sun J, Gong X, Purow B, Zhao Z (2012) Uncovering microRNA and transcription factor mediated regulatory networks in glioblastoma. PLoS Comput Biol 8:e1002488

    Article  PubMed  CAS  Google Scholar 

  26. Zhou X, Marian C, Makambi KH, Kosti O, Kallakury BV, Loffredo CA, Zheng YL (2012) microRNA-9 as potential biomarker for breast cancer local recurrence and tumor estrogen receptor status. PLoS One 7:e39011

    Article  PubMed  CAS  Google Scholar 

Download references

Funding

This work was funded by National Natural Science Foundation of China (NO. 81272776).

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yunqing Li or Guodong Gao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, Z., Wang, L., Li, G. et al. Increased expression of microRNA-9 predicts an unfavorable prognosis in human glioma. Mol Cell Biochem 384, 263–268 (2013). https://doi.org/10.1007/s11010-013-1805-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1805-5

Keywords

Navigation