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Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines.


ABSTRACT: BACKGROUND:Osimertinib (AZD9291), a third-generation EGFR-tyrosine kinase inhibitor, can effectively prolong survival in non-small cell lung cancer (NSCLC) patients with EGFR mutations, particularly T790M mutations; however, acquired resistance to AZD9291 is inevitable, thus exploration of the targets of resistance is urgent. METHODS:Considering the important role of circular RNAs (circRNAs) in cancers, we established AZD9291-resistant NSCLC cell lines (H1975/AZDR and HCC827/AZDR) and used microarray analysis to determine the circRNA expression profiles of the cells. The H1975/AZDR and HCC827/AZDR cell lines were induced by gradually increasing the drug concentration. CircRNA microarray expression profiles were obtained from H1975, HCC827, H1975/AZDR, and HCC827/AZDR cells and validated by quantitative reverse transcription PCR. Expression data were analyzed bioinformatically. RESULTS:The H1975/AZDR and HCC827/AZDR cell lines were successfully established. The half-maximal inhibitory concentration and the invasion ability of H1975/AZDR and HCC827/AZDR cells were significantly enhanced. The proliferation rates of H1975/AZDR and HCC827/AZDR were much lower than H1975 and HCC827. Microarray analysis identified 15?504 circRNAs differentially expressed in H1975, HCC827, H1975/AZDR, and HCC827/AZDR cells. Among them, 7966 were upregulated and 7538 were downregulated more than two-fold. We predicted the possible miRNAs of the top dysregulated circRNAs. Furthermore, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the most modulated circRNAs regulate several cancers and cancer-related pathways. CONCLUSION:Our results reveal that circRNAs may play a role in NSCLC AZD9291 resistance and might be a promising molecular target candidate for gene therapy.

SUBMITTER: Chen T 

PROVIDER: S-EPMC6449233 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines.

Chen Tianxiang T   Luo Jizhuang J   Gu Yu Y   Huang Jia J   Luo Qingquan Q   Yang Yunhai Y  

Thoracic cancer 20190318 4


<h4>Background</h4>Osimertinib (AZD9291), a third-generation EGFR-tyrosine kinase inhibitor, can effectively prolong survival in non-small cell lung cancer (NSCLC) patients with EGFR mutations, particularly T790M mutations; however, acquired resistance to AZD9291 is inevitable, thus exploration of the targets of resistance is urgent.<h4>Methods</h4>Considering the important role of circular RNAs (circRNAs) in cancers, we established AZD9291-resistant NSCLC cell lines (H1975/AZDR and HCC827/AZDR)  ...[more]

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