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LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human glioblastoma multiforme

  • Original Article - Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Objectives

To study the expression profiles of lncRNA and mRNA in glioblastoma multiforme (GBM) and to find potential core genes in the pathogenesis of this high malignant disease.

Methods

Agilent Microarray (Arrystar v2.0) was used to detect the expressions of 33,045 lncRNAs and 30,215 coding transcripts in 5 GBM and 5 normal brain samples. Differentially expressed lncRNAs and mRNAs were identified through Volcano Plot filtering. The expressions of six lncRNAs were further detected by qPCR to validate the results of microarray. The function of differential mRNA was determined by pathway and GO analysis, and the function of lncRNAs was studied by subgroup analysis and by their physical or functional relationships with corresponding mRNAs.

Results

A total of 815 lncRNAs and 738 mRNAs are found to be differentially expressed between the GBM and normal brain groups. With the expression of these differentially expressed genes, the two group samples could be clearly differentiated. The result of qPCR has showed a good consistency with the microarray, thus proving the accuracy of the microarray data. GO and Pathway analyses have proved that the functions of differentially expressed mRNAs in GBM related closely with many processes that important in the cancer pathogenesis. Core lncRNAs and mRNAs that may play important roles in the pathogenesis of GBM are revealed and listed according to various methods.

Conclusion

The GBM shows an aberrant expression profile of lncRNA and mRNA. Potential core genes are revealed by the lncRNA and mRNA interaction study based on transcriptome profiles in GBM.

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Abbreviations

GBM:

Glioblastoma multiforme

LncRNA:

Long noncoding RNA

HOTAIR:

HOX antisense intergenic RNA

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

MEG3:

Maternally expressed gene 3

SAGE:

Serial analyses of gene expression

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

FDR:

False discovery rate

GO:

Gene Ontology

KEGG:

Kyoto encyclopedia of genes and genomes

RVM t test:

Random variance model t test

lincRNAs:

Large intervening noncoding RNAs

PRC2:

The polycomb complex 2

ITSN1:

Intersectin 1

UCSC:

University of California, Santa Cruz

HEIH:

LncRNA high expression in hepatocellular carcinoma

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Acknowledgments

This study was supported by the National “863” High Technique Project (2007AA02Z483), National Natural Science Foundation of China (30930094, 81101908, 81272781, 30973076), Program for academic leaders in health sciences (No. XBR2011030) and “Shu Guang” project (No. 11SG37) in Shanghai. We want to thank Yanfen Ge and her colleagues at KangCheng Bio-tech Inc., and Qi Li and his colleagues at Gminix Company, for the assistance in bioinformatic analysis and many other help during the course of this study.

Conflict of interest

None.

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Authors and Affiliations

  1. Neurosurgery Research Institution of Shanghai, Department of Neurosurgery, ChangZheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, 200003, China

    Yong Yan, Lei Zhang, Ying Jiang, Tao Xu, Qiyong Mei, Hongxiang Wang, Rong Qin, Yongxiang Zou, Guohan Hu, Juxiang Chen & Yicheng Lu

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  1. Yong Yan
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  2. Lei Zhang
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Corresponding authors

Correspondence to Juxiang Chen or Yicheng Lu.

Additional information

Yong Yan and Lei Zhang have contributed equally to the article.

Electronic supplementary material

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432_2014_1861_MOESM1_ESM.tif

Supplementary material 1 (TIFF 1201 kb) Figure S1: GO analysis of differential expressed (A, C, and E, up-regulated; B, D, and F, down-regulated) mRNA in GBMs. A and B, Biological process; C and D, Cellular component; E and F, Molecular function

432_2014_1861_MOESM2_ESM.tif

Supplementary material 2 (TIFF 9904 kb) Figure S2: Gene co-expression network of the normal brain. The solid round spots stand for the mRNAs, the Hexagon with a circle spots stand for the lncRNAs. The lines between spots stand for the relationship between the genes. The spot size is on behalf of the capability of a gene to act with its adjacent genes

432_2014_1861_MOESM3_ESM.tif

Supplementary material 3 (TIFF 10098 kb) Figure S3: Gene co-expression network of the GBM. The solid round spots stand for the mRNAs, the Hexagon with a circle spots stand for the lncRNAs. The lines between spots stand for the relationship between the genes. The spot size is on behalf of the capability of a gene to act with its adjacent genes

Supplementary material 4 (DOC 30 kb)

Supplementary material 5 (XLS 717 kb)

Supplementary material 6 (XLS 898 kb)

Supplementary material 7 (DOC 28 kb)

Supplementary material 8 (DOC 19 kb)

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Yan, Y., Zhang, L., Jiang, Y. et al. LncRNA and mRNA interaction study based on transcriptome profiles reveals potential core genes in the pathogenesis of human glioblastoma multiforme. J Cancer Res Clin Oncol 141, 827–838 (2015). https://doi.org/10.1007/s00432-014-1861-6

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