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Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme

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Tumor Biology

Abstract

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.

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Acknowledgments

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).

Authors’ contribution

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.

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Authors and Affiliations

  1. Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China

    He-ming Wu, Han-dong Wang, Yong Tang, You-wu Fan, Yue-bing Hu, Mamatemin Tohti, Xiao-ke Hao, Wu-ting Wei & Yong Wu

  2. Department of Neurosurgery, Nanjing Jingdu Hospital, No. 34, Biao 34, Yanggongjing Road, Nanjing, 210002, Jiangsu Province, China

    He-ming Wu

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  1. He-ming Wu
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  7. Xiao-ke Hao
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Correspondence to Han-dong Wang.

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Supplementary materials Fig 5

miRNA-target gene-pathway network analysis. Red round rectangle nodes represented miRNAs, grey circle nodes represented target genes and green triangle nodes represented enrichment pathways. Edges indicated the inhibitive effect of miRNAs on target genes. (JPEG 507 kb)

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(JPEG 928 kb)

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Wu, Hm., Wang, Hd., Tang, Y. et al. Differential expression of microRNAs in postoperative radiotherapy sensitive and resistant patients with glioblastoma multiforme. Tumor Biol. 36, 4723–4730 (2015). https://doi.org/10.1007/s13277-015-3121-z

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  • DOI: https://doi.org/10.1007/s13277-015-3121-z

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