Top

Published in:

01-06-2013 | Laboratory Investigation

Expression level of human miR-34a correlates with glioma grade and prognosis

Authors: Haifeng Gao, Hongyang Zhao, Wei Xiang

Published in: Journal of Neuro-Oncology | Issue 2/2013

Abstract

The aim of this study is to investigate the expression level of microRNA-34a (miR-34a) in glioma patients and its significance for predicting the prognosis of glioma. In this study, we examined the expression of miR-34a in glioma tissues of various World Health Organization (WHO) grades and explored the association between miR-34a expression and clinical and pathological parameters of glioma patients. We found that the tissues from high-grade gliomas (grade III and IV) had much lower miR-34a expression compared to normal brain tissues. The results of a 72-month follow-up in 146 glioma patients further demonstrated that miR-34a expression levels positively correlated with tumor WHO grades. Additionally, in the patients with grade III and IV gliomas, lower miR-34a expression correlated with worse progression-free survival and overall survival. Univariate and multivariate analysis revealed that miR-34a was an independent prognostic indicator for glioma. Additionally, we explored the correlation between miR-34a expression and p53 status and Bcl-2 expression in grade III and IV glioma tissues. Wild-type p53 tumors displayed significantly higher miR-34a expression level than mutant p53 tumors. In addition, glioma tissues with high miR-34a expression had dramatically lower Bcl-2 expression levels than tissues with low miR-34a expression. These findings indicate the role of miR-34a in tumor progression may be closely associated with p53 mutation and inversely correlated to Bcl-2 expression. In conclusion, our work presents comprehensive evidence for miR-34a expression as a novel and potentially useful signature for predicting prognosis of glioma.

Huang TT, Sarkaria SM, Cloughesy TF, Mischel PS (2009) Targeted therapy for malignant glioma patients: lessons learned and the road ahead. Neurotherapeutics 6:500–512PubMedCrossRef

Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J et al (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773PubMedCrossRef

Hermeking H (2010) The miR-34 family in cancer and apoptosis. Cell Death Differ 17:193–199PubMedCrossRef

He L, He X, Lim LP, de Stanchina E, Xuan Z, Liang Y et al (2007) A microRNA component of the p53 tumour suppressor network. Nature 447:1130–1134PubMedCrossRef

Chen QR, Yu LR, Tsang P, Wei JS, Song YK, Cheuk A et al (2011) Systematic proteome analysis identifies transcription factor YY1 as a direct target of miR-34a. J Proteome Res 10:479–487PubMedCrossRef

Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E et al (2009) MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res 69:7569–7576PubMedCrossRef

Weeraratne SD, Amani V, Neiss A, Teider N, Scott DK, Pomeroy SL et al (2011) miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol 13:165–175PubMedCrossRef

Silber J, Jacobsen A, Ozawa T, Harinath G, Pedraza A, Sander C et al (2012) miR-34a repression in proneural malignant gliomas upregulates expression of its target PDGFRA and promotes tumorigenesis. PLoS ONE 7:e33844PubMedCrossRef

Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 3:1101–1108PubMedCrossRef

10.

Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L et al (2009) MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS ONE 4:e6816PubMedCrossRef

11.

Krypuy M, Ahmed AA, Etemadmoghadam D, Hyland SJ, Australian Ovarian Cancer Study G, DeFazio A et al (2007) High resolution melting for mutation scanning of TP53 exons 5–8. BMC cancer 7:168PubMedCrossRef

12.

Chen Z, An S, Xie Z, Yan H, Chen J, Su J et al (2011) High resolution melting analysis for detecting p53 gene mutations in patients with non-small cell lung cancer. Chin J Lung Cancer 14:767–773

13.

Margraf LR, Gargan L, Butt Y, Raghunathan N, Bowers DC (2011) Proliferative and metabolic markers in incompletely excised pediatric pilocytic astrocytomas: an assessment of 3 new variables in predicting clinical outcome. Neuro Oncol 13:767–774PubMedCrossRef

14.

Catt S, Chalmers A, Fallowfield L (2008) Psychosocial and supportive-care needs in high-grade glioma. Lancet Oncol 9:884–891PubMedCrossRef

15.

Chang TC, Wentzel EA, Kent OA, Ramachandran K, Mullendore M, Lee KH et al (2007) Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol Cell 26:745–752PubMedCrossRef

16.

Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A et al (2007) Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6:1586–1593PubMedCrossRef

17.

Bommer GT, Gerin I, Feng Y, Kaczorowski AJ, Kuick R, Love RE et al (2007) p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr Biol 17:1298–1307PubMedCrossRef

18.

Welch C, Chen Y, Stallings RL (2007) MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 26:5017–5022PubMedCrossRef

19.

Tazawa H, Tsuchiya N, Izumiya M, Nakagama H (2007) Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci USA 104:15472–15477PubMedCrossRef

20.

Genovese G, Ergun A, Shukla SA, Campos B, Hanna J, Ghosh P et al (2012) microRNA regulatory network inference identifies miR-34a as a novel regulator of TGF-beta signaling in glioblastoma. Cancer Discov 2:736–749PubMedCrossRef

21.

Fels C, Schafer C, Huppe B, Bahn H, Heidecke V, Kramm CM et al (2000) Bcl-2 expression in higher-grade human glioma: a clinical and experimental study. J Neuro Oncol 48:207–216CrossRef

22.

Xu T, Qin R, Zhou J, Yan Y, Lu Y, Zhang X et al (2012) High bone sialoprotein (BSP) expression correlates with increased tumor grade and predicts a poorer prognosis of high-grade glioma patients. PLoS ONE 7:e48415PubMedCrossRef

23.

Gao H, Yu B, Yan Y, Shen J, Zhao S, Zhu J, et al (2012) Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis. J Neurosurg. doi:10.3171/2012.9.JNS112134.

24.

Chen F, Hu SJ (2012) Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol 26:79–86PubMedCrossRef

25.

Mraz M, Malinova K, Kotaskova J, Pavlova S, Tichy B, Malcikova J et al (2009) miR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalities. Leukemia 23:1159–1163PubMedCrossRef

26.

Cole KA, Attiyeh EF, Mosse YP, Laquaglia MJ, Diskin SJ, Brodeur GM et al (2008) A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res 6:735–742PubMedCrossRef

27.

Fujita Y, Kojima K, Hamada N, Ohhashi R, Akao Y, Nozawa Y et al (2008) Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells. Biochem Biophys Res Commun 377:114–119PubMedCrossRef

28.

Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D et al (2008) Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer 8:266PubMedCrossRef

Title: Expression level of human miR-34a correlates with glioma grade and prognosis
Authors: Haifeng Gao
Hongyang Zhao
Wei Xiang
Publication date: 01-06-2013
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 2/2013
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-013-1119-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Expression level of human miR-34a correlates with glioma grade and prognosis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2013

Single-nucleotide polymorphisms of allergy-related genes and risk of adult glioma

The role of the CXCR4 cell surface chemokine receptor in glioma biology

Hypoxia-induced expression of VE-cadherin and filamin B in glioma cell cultures and pseudopalisade structures

Computerized assessment of cognitive late effects among adolescent brain tumor survivors

Prognostic significance of IDH mutation in adult low-grade gliomas: a meta-analysis

Interferon regulatory factor 3 alters glioma inflammatory and invasive properties