Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and more resistant to radiotherapy. However, hetero-radiosensitivity occurs in different patients. MicroRNAs (miRNAs) play important roles in the initiation and progression of a multitude of tumors. The study aims to examine the different microRNAs expression profiles of postoperative radiotherapy sensitive and resistant patients with GBM, to make an inquiry about their potential role and discover a certain set of radio-sensitivity markers. Three paired samples from six GBM patients who had only been treated with postoperative radiotherapy were selected, and then, they were divided into radiotherapy sensitive group and resistant group according to their overall survivals, local recurrence rates, and Karnofsky Performance Scale scores. Expression profiles of miRNAs in these two groups were determined by the method of microarray assay. Comparing with resistant patients, 13 miRNAs were significantly upregulated and 10 miRNAs were greatly downregulated in sensitive group. Among them, four miRNAs were validated by quantitative RT-PCR. The differentially expressed miRNAs and their putative target genes were revealed by bioformatic analysis to play a role in cell signaling, proliferation, aging, and death. High-enrichment pathway analysis identified that some classical pathways participated in numerous metabolic processes, especially in cell cycle regulation, such as mTOR, MAPK, TGF-beta, and PI3K-Akt signaling pathways. Our research will contribute to identifying clinical diagnostic markers and therapeutic targets in the treatment of GBM by postoperative radiotherapy.
MicroRNA Glioblastoma Radiation Sensitivity
This is a preview of subscription content, log in to check access
This work was supported by the grants from the National Nature Science Foundation of China under Grant (No. 81301180, 31200633) and China Postdoctoral Science Foundation funded project under Grant (No. 2014M562665).
Han-dong Wang and He-ming Wu were responsible for the conception and design of the study. Yong-Tang, You-wu Fan, Wu-ting Wei, and Yong Wu contributed to the samples acquisition. Mamatemin Tohti and Xiao-ke Hao were responsible for data analysis. He-ming Wu and Yue-bing Hu were responsible for the interpretation of findings and the drafting of the manuscript. All authors critically reviewed the content and approved the final version for publication.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. European Organisation for R, Treatment of Cancer Brain T, Radiotherapy G, National Cancer Institute of Canada Clinical Trials G: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.CrossRefPubMedGoogle Scholar
Gonzalez-Gomez P, Sanchez P, Mira H. Micrornas as regulators of neural stem cell-related pathways in glioblastoma multiforme. Mol Neurobiol. 2011;44:235–49.CrossRefPubMedGoogle Scholar
Joki T, Carroll RS, Dunn IF, Zhang J, Abe T, Black PM. Assessment of alterations in gene expression in recurrent malignant glioma after radiotherapy using complementary deoxyribonucleic acid microarrays. Neurosurgery. 2001;48:195–201. discussion 201–192.PubMedGoogle Scholar
Chaudhry MA, Sachdeva H, Omaruddin RA. Radiation-induced micro-RNA modulation in glioblastoma cells differing in DNA-repair pathways. DNA Cell Biol. 2010;29:553–61.CrossRefPubMedGoogle Scholar
Novakova J, Slaby O, Vyzula R, Michalek J. Microrna involvement in glioblastoma pathogenesis. Biochem Biophys Res Commun. 2009;386:1–5.CrossRefPubMedGoogle Scholar
Zhang W, Zhang J, Yan W, You G, Bao Z, Li S, et al. Whole-genome microRNA expression profiling identifies a 5-microrna signature as a prognostic biomarker in Chinese patients with primary glioblastoma multiforme. Cancer. 2013;119:814–24.CrossRefPubMedGoogle Scholar
Cellini F, Morganti AG, Genovesi D, Silvestris N, Valentini V. Role of microRNA in response to ionizing radiations: Evidences and potential impact on clinical practice for radiotherapy. Molecules. 2014;19:5379–401.CrossRefPubMedGoogle Scholar
Wang XC, Du LQ, Tian LL, Wu HL, Jiang XY, Zhang H, et al. Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer. Lung Cancer. 2011;72:92–9.CrossRefPubMedGoogle Scholar
Teo MT, Landi D, Taylor CF, Elliott F, Vaslin L, Cox DG, et al. The role of microRNA-binding site polymorphisms in DNA repair genes as risk factors for bladder cancer and breast cancer and their impact on radiotherapy outcomes. Carcinogenesis. 2012;33:581–6.CrossRefPubMedGoogle Scholar
Liu S, Yin F, Zhang J, Wicha MS, Chang AE, Fan W, et al. Regulatory roles of miRNA in the human neural stem cell transformation to glioma stem cells. J Cell Biochem. 2014;115:1368–80.CrossRefPubMedGoogle Scholar
Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, et al. Extensive modulation of a set of microRNAs in primary glioblastoma. Biochem Biophys Res Commun. 2005;334:1351–8.CrossRefPubMedGoogle Scholar
Niemoeller OM, Niyazi M, Corradini S, Zehentmayr F, Li M, Lauber K, et al. Microrna expression profiles in human cancer cells after ionizing radiation. Radiat Oncol. 2011;6:29.CrossRefPubMedPubMedCentralGoogle Scholar
Kozomara A, Griffiths-Jones S. Mirbase: Annotating high confidence microRNAs using deep sequencing data. Nucleic Acids Res. 2014;42:D68–73.CrossRefPubMedGoogle Scholar
Chen G, Zhu W, Shi D, Lv L, Zhang C, Liu P, et al. Microrna-181a sensitizes human malignant glioma u87mg cells to radiation by targeting bcl-2. Oncol Rep. 2010;23:997–1003.PubMedGoogle Scholar
Ruan WK, Shi Y, Wang J. Expression of miR-129-5p in glioma and its effect on glycometabolism and growth of human glioma cells. Jiangsu Med J. 2013;39:48–54.Google Scholar