MiR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma.
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ABSTRACT:
SUBMITTER: Zhang WC
PROVIDER: S-EPMC6750230 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
miR-147b-mediated TCA cycle dysfunction and pseudohypoxia initiate drug tolerance to EGFR inhibitors in lung adenocarcinoma.
Zhang Wen Cai WC Wells Julie M JM Chow Kin-Hoe KH Huang He H Yuan Min M Saxena Tanvi T Melnick Mary Ann MA Politi Katerina K Asara John M JM Costa Daniel B DB Bult Carol J CJ Slack Frank J FJ
Nature metabolism 20190408 4
Drug-tolerance is an acute defense response prior to a fully drug-resistant state and tumor relapse, however there are few therapeutic agents targeting drug-tolerance in the clinic. Here we show that miR-147b initiates a reversible tolerant-state to the EGFR inhibitor osimertinib in non-small cell lung cancer. With miRNA-seq analysis we find that miR-147b is the most upregulated microRNA in osimertinib-tolerant and <i>EGFR</i> mutated lung cancer cells. Whole transcriptome analysis of single-cel ...[more]
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