DNA methylome analysis of DNA methyltransferase inhibitor reagent-treated lung cancer cells

Purpose: Epigenetic drug DNA methyltransferase inhibitors (DNMTis) are immunomodulating agents that may sensitize cancer cells to immune cell attack. However, it is still unclear how DNMTi affects cancer cells to the killing by immune cells. We therefore try to uncover the alternations of genomic DNA methylation after DNMTi treatment of cancer cells. Methods: Six human lung cancer cell lines (A549, H1299, CL1-0, CL1-5, H1792, PC9) before (Mock) and after (DAC) treatement with 100 nM decitabine (DAC) for 72 hours followed by growing in drug-free medium for three days were subjected to Illumina MethylationEPIC microarray analysis. Results: DNA methylome analysis reveals DNMTi-induced DNA demethylation at transcription start site (TSS)-flanking regions of several actin, intermediate filament and microtubule molecules in human lung cancer cell lines. Conclusion: Decitabine primes lung cancer cells to γδ T cell-mediated killing through regulating cytoskeleton associated genes potentially involved in immune synapse formation. Methylome altenation analysis between control (Mock) and decitabine (DAC) treated human lung cancer cell lines (A549, H1299, CL1-0, CL1-5, H1792, PC9).