Genomic profiling of long non-coding RNA and mRNA expression associated with acquired temozolomide resistance in glioblastoma cells

Zeng,Huijun; Xu,Ningbo; Liu,Yanting; Liu,Boyang; Yang,Zhao; Fu,Zhao; Lian,Changlin; Guo,Hongbo

doi:10.3892/ijo.2017.4033

Genomic profiling of long non-coding RNA and mRNA expression associated with acquired temozolomide resistance in glioblastoma cells

Authors:
- Huijun Zeng
- Ningbo Xu
- Yanting Liu
- Boyang Liu
- Zhao Yang
- Zhao Fu
- Changlin Lian
- Hongbo Guo
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Affiliations: The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei 443002, P.R. China
Published online on: June 7, 2017 https://doi.org/10.3892/ijo.2017.4033
Pages: 445-455
Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Temozolomide (TMZ) is an alkylating chemotherapeutic agent widely used in anti-glioma treatment. However, acquired TMZ resistance represents a major clinical challenge that leads to tumor relapse or progress. This study investigated the genomic profiles including long non-coding RNA (lncRNA) and mRNA expression associated with acquired TMZ resistance in glioblastoma (GBM) cells in vitro. The TMZ-resistant (TR) of GBM sub-cell lines were established through repetitive exposure to increasing TMZ concentrations in vitro. The differentially expressed lncRNAs and mRNAs between the parental U87 and U87TR cells were detected by human lncRNA microarray method. In this study, we identified 2,692 distinct lncRNAs demonstrating >2-fold differential expression with 1,383 lncRNAs upregulated and 1,309 lncRNAs downregulated. Moreover, 4,886 differential mRNAs displayed 2,933 mRNAs upregulated and 1,953 mRNAs downregulated. Further lncRNA classification and subgroup analysis revealed the potential functions of the lncRNA-mRNA relationship associated with the acquired TMZ resistance. Gene ontology and pathway analysis on mRNAs showed significant biological regulatory genes and pathways involved in acquired TMZ resistance. Moreover, we found the ECM‑receptor interaction pathway was significantly downregulated and ECM related collagen Ι, fibronectin, laminin and CD44 were closely associated with the TR phenotype in vitro. Our findings indicate that the dysregulated lncRNAs and mRNAs identified in this work may provide novel targets for overcoming acquired TMZ resistance in GBM chemotherapy.

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