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Gene expression profiling analysis reveals that DLG3 is down-regulated in glioblastoma

  • Laboratory Investigation
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Abstract

Glioblastoma multiforme (GBM) is the most malignant glioma. In the current study, 149 astrocytoma gene expression datasets were classified by prediction analysis of microarray. Strikingly, disks large homolog 3 (DLG3), a membrane-associated guanylate kinase-family gene, had the highest score in the GBM subset. DLG3 mRNA expression is significantly down-regulated in GBM relative to normal tissue and grade II or grade III astrocytoma according to the results of real-time polymerase chain reaction, and its protein expression shows an obvious difference by immunohistochemistry. Further assays show that DLG3 over-expression induces mitotic cell cycle arrest and apoptosis, and it inhibits proliferation and migration. However, DLG3 over-expression has almost no affect on invasion. The DLG3 protein expression in human brain GBM tissue and its effects on GBM cell invasion were not expected. Our data suggest that DLG3 is down-regulated in this cancer type. To our knowledge, this is the first report to clearly demonstrate the possible involvement of DLG3 in GBM.

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Acknowledgments

The authors wish to express their sincere appreciation to Dr. Yangkun Wang and all of the pathologists in the department of pathology at the No. 150 Central Hospital of PLA. We thank them for their support in the specimen pathological diagnosis and grading. Special thanks are due to the reviewers, whose critical eye and enlightened mentoring were instrumental and inspiring.

Conflict of interests

All of the authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. The Anal-Colorectal Surgery Institute, No. 150 Central Hospital of PLA, Luoyang, 471031, Henan, China

    Zhongyu Liu, Zhiqiang Yao & Chunfang Gao

  2. The School of Life Science, Sichuan University, Chengdu, 610000, Sichuan, China

    Yulong Niu

  3. The Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing, 400016, China

    Mengyu Xie & Youquan Bu

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  1. Zhongyu Liu
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  2. Yulong Niu
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  5. Zhiqiang Yao
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Corresponding author

Correspondence to Chunfang Gao.

Additional information

Zhongyu Liu and Yulong Niu have contributed equally to this work.

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Supplementary Fig. 1

Array intensity distributions (a) and outlier detection for boxplots (b). a Graph A shows boxplots representing the summaries of the signal intensity distributions of the arrays. Each box corresponds to one array. Typically, one expects the boxes to have similar positions and widths. If the distribution of an array is very different from the others, this may indicate an experimental problem. Outlier detection was performed by computing the Kolmogorov-Smirnov statistic Ka between each array’s distribution and the distribution of the pooled data. b Graph B shows a bar chart of the Kolmogorov-Smirnov statistic Ka, and the outlier detection criterion from the previous figure. The bars are shown in the original order of the arrays. Based on the distribution of the values across all arrays, a threshold of 0.319 was determined, which is indicated by the vertical line. None of the arrays exceeded the threshold; therefore, none was considered to be an outlier. Supplementary material 1 (PNG 1641 kb)

Supplementary Fig. 2

Immunohistochemical validation of DLG3 down-regulation in astrocytomas. A section from normal brain tissue (a), from DA tissue (b) from AA tissue (c) and from GBM tissue for staining (d). The staining decreases from normal to GBM.. Supplementary material 2 (JPEG 3720 kb)

Supplementary material 3 (XLS 54 kb)

Supplementary material 4 (XLS 29 kb)

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Liu, Z., Niu, Y., Xie, M. et al. Gene expression profiling analysis reveals that DLG3 is down-regulated in glioblastoma. J Neurooncol 116, 465–476 (2014). https://doi.org/10.1007/s11060-013-1325-x

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  • DOI: https://doi.org/10.1007/s11060-013-1325-x

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