Genomic profiling of long non-coding RNA and mRNA expression associated with acquired temozolomide resistance in glioblastoma cells.
Genomic profiling of long non-coding RNA and mRNA expression associated with acquired temozolomide resistance in glioblastoma cells.
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与胶质母细胞瘤细胞获得性替莫唑胺耐药相关的长非编码 RNA 和 mRNA 表达的基因组分析
DOI：
10.3892/ijo.2017.4033
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发表时间：
2017-08
影响因子：
5.2
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Zeng H;Xu N;Liu Y;Liu B;Yang Z;Fu Z;Lian C;Guo H
替莫唑胺(TMZ)是一种广泛用于抗胶质瘤治疗的烷基化化疗药物。然而，获得性TMZ耐药性是导致肿瘤复发或进展的主要临床挑战。本研究在体外研究了胶质母细胞瘤(GBM)细胞中与获得性TMZ耐药相关的基因组谱，包括长非编码RNA(LncRNA)和mRNA的表达。通过体外重复暴露于不同浓度的TMZ，建立了耐TMZ的GBM亚细胞系。用人LncRNA微阵列技术检测亲本细胞U87和U87TR之间的差异表达。在这项研究中，我们鉴定了2,692个差异表达的lncRNA，其中1,383个上调，1,309个下调。此外，4,886个差异mRNAs显示2,933个mRNAs上调，1,953个mRNAs下调。进一步的lncRNA分类和亚群分析揭示了与获得性TMZ抗性相关的lncRNA-mRNA关系的潜在功能。对mRNAs的基因本体论和途径分析表明，与获得性TMZ抗性有关的重要生物调控基因和途径。此外，我们还发现，ECM-受体相互作用途径在体外显著下调，ECM相关的I型胶原、纤维连接蛋白、层粘连蛋白和CD44与TR表型密切相关。我们的发现表明，本工作中发现的失调的lncRNAs和mRNAs可能为克服GBM化疗中获得性TMZ耐药性提供新的靶点。
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 I, 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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影响因子：
37.3
作者：
Gibb EA;Brown CJ;Lam WL
通讯作者：
Lam WL
影响因子：
5.2
作者：
He, Dong-Xu;Zhang, Guang-Yuan;Ma, Xin
通讯作者：
Ma, Xin
影响因子：
9.7
作者：
Munoz, Jessian L.;Walker, Nykia D.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela
影响因子：
50.5
作者：
Schaich, M.;Kestel, L.;Krex, D.
通讯作者：
Krex, D.
影响因子：
3.9
作者：
Idbaih, Ahmed;Silva, Rosana Carvalho;Delattre, Jean-Yves
通讯作者：
Delattre, Jean-Yves