Microarray expression profiles and bioinformatics analysis of mRNAs, lncRNAs, and circRNAs in the secondary temozolomide-resistant glioblastoma.

ABSTRACT

Temozolomide is a first line anti-tumor drug used for the treatment of patients with Glioblastoma multiforme (GBM). However, the drug resistance to temozolomide limits its clinical application. Therefore, novel strategies to overcome chemoresistance are desperately needed for improved treatment of human GBM. Here, we simultaneously detected, for the first time, the expression profiles of mRNAs, lncRNAs, and circRNAs in three pairs of secondary temozolomide-resistant glioblastoma (STRG) and matched primary glioblastoma tissues by microarrays. Using these data, we discovered a total of 92 mRNA, 299 lncRNAs and 53 circRNAs were altered in human glioma tissue after chemotherapy with temozolomide. The functions of differentially expressed lncRNAs, circRNAs were annotated by analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The results showed that the highest enriched GO terms of the upregulated lncRNAs were embryonic forelimb morphogenesis (BP), extracellular space (CC), and serine-type endopeptidase activity (MF). Meanwhile, GO0035360(BP), PRC1 complex (CC), and ubiquitin-protein transferase activity (MF) were the highest enriched GO terms targeted by downregulated lncRNAs. The NF-kappa B signaling pathway were significantly enriched in the STRG. However, circRNAs highest enriched GO term was viral process, chromosome, and protein transporter activity, respectively. KEGG pathway analysis showed that circRNAs in the network were enriched in ErbB signaling pathway. Furthermore, we also predicted the potential role of these differentially expressed ncRNAs and constructed a network of lncRNAs-mRNAs and circRNAs-miRNAs to show their interactions. After a series of bioinformatics analyses, we found that low expression of NONHSAT163779 and high expression of circ_0043949 are closely related to the chemoresistance of STRG. Our findings revealed the alteration of expression patterns of mRNAs, lncRNAs, and circRNAs in the secondary temozolomide-resistant glioblastoma for the first time. NONHSAT163779 and hsa_circ_0043949 might be potential therapeutic targets and prognostic biomarkers for the treatment of glioblastoma.