Identification and functional characterization of lncRNAs acting as ceRNA involved in the malignant progression of glioblastoma multiforme

摘要

Glioblastoma multiforme (GBM) is the most common brain malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and involved in pathogenesis, progression and metastasis of tumors. In particular, lncRNAs can function as competing endogenous RNAs (ceRNAs). The functional roles of lncRNA associated-ceRNAs in GBM are not fully understood. Human Exon 1.0 Microarray (Affymetrix) and Human MicroRNA Microarray (Agilent) were used to detect the expression of 955 microRNAs (miRNAs), 33,125 lncRNAs, and 17,453 mRNAs in 8 GBM and 8 normal brain samples. The function of differential mRNA was determined by Gene Ontology (GO) and pathway analysis. The distinctly expressed miRNAs, lncRNAs and mRNAs were subjected to construct miRNA-lncRNA-mRNA interaction network. The expression of miRNAs, lncRNAs and mRNAs in GBM tissues vs. normal brain tissues was examined by quantitative real-time RT-PCR. A total of 41 miRNAs, 398 lncRNAs and 1,995 mRNAs were found to be differentially expressed between the GBM and normal brain groups. GO and pathway analyses had proven that the functions of differentially expressed mRNAs in GBM related closely with many processes important in the cancer pathogenesis. Fifty-five lncRNAs acting as ceRNAs were identified based on the miRNA-lncRNA-mRNA interaction network. The potential roles of the 39 ceRNAs were revealed, which participated in 23 diverse cancer biological pathways, including proliferation, cell apoptosis, adhesion, angiogenesis and metastasis. The identified sets of miRNAs, lncRNAs and mRNAs specific to GBM were verified by qRT-PCR experiment in GBM samples. Our study predicts the biological functions of a multitude of 1ncRNA associated-ceRNAs in GBM. Moreover, our study provides a road map for the identification and analysis of 1ncRNA acting as ceRNA in tumors.