Transcriptomics,Genomics

Dataset Information

36

Non-coding mechanisms of tolerance, persistence and resistance to EGFR inhibition in lung cancer [microRNA-seq]


ABSTRACT: Purpose: To characterize microRNA signatures for tolerance, persistence and resistance to EGFR tyrosine kinase inhibitors (TKIs) in human lung cancer. Methods: microRNA profiles of gefitinib- and osimertinib-tolerant cells in PC9 and HCC827 cells were generated by deep microRNA sequencing using Illumina. In addition, microRNA profiles of PC9 subpopulations cells with characterizations of persistence and resistance to gefitinib were generated by deep microRNA sequencing. The mappable reads were aligned to the human genome and miRbase using Bowtie. Results: We identified a specific microRNA profile distinguishing tolerance, persistence and resistance to gefitinib or osimertinib from parental human lung cancer cells with mutated EGFR. The expressions of those microRNAs in lung cancer cells were validated by qRT-PCR. Functionally, knocking down top-upregulated microRNAs reduced the tolerance, persistence and resistance to gefitinib or osimertinib in those tolerant and resistant cells. Conversely, overexpression of those microRNAs enhanced the tolerance and resistance to EGFR inhibition in cells sensitive to gefitinib and osimertinib. Conclusions: Our work identifies a panel of microRNAs that mediate EGFR-TKI tolerance and resistance in lung cancer. Our study provides potential non-coding targets to improve the efficacy of EGFR-TKIs therapy in cancer pagtients. Overall design: microRNA profiles of gefitinib and osimertinib tolerant cells in PC9 (PC9GTR and PC9OTR) and HCC827 (HCC827GTR and HCC827OTR) were generated by deep sequencing using Illumina. In addition, microRNA profiles of PC9 persisters and resistant cells treated by gefitinib and WZ4002 were generated by deep sequencing.

INSTRUMENT(S): Illumina HiSeq 2500 (Homo sapiens)

SUBMITTER: Wen Cai Zhang  

PROVIDER: GSE103352 | GEO | 2018-01-11

SECONDARY ACCESSION(S): PRJNA401843

REPOSITORIES: GEO

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