Super enhancer associated is a new potential biomarker in lung adenocarcinoma.

PURPOSE

Tyrosine kinase inhibitors (TKIs) are widely used to treat lung adenocarcinoma patients with mutations or -fusions. However, patients with wild-type genes or TKIs-resistant mutations lack effective therapeutic targets. Extensive studies reveal that super enhancer (SE), a large -regulatory element, is associated with key oncogenes in a variety of cancers. By comparing the effect of SE on lung adenocarcinoma cell lines with normal cell line, this work attempts to find new biomarkers and potential therapeutic targets for lung adenocarcinoma.

EXPERIMENTAL DESIGN

Chromatin Immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) of H3K27ac (acetylation on lysine 27 of histone 3) was performed in lung adenocarcinoma cell lines SPC-A1 and SCH-1153. The differences in SE distribution were then analyzed among SPC-A1, SCH-1153, A549 and normal human lung fibroblasts (NHLF) to identify SE-associated oncogenes. The expression of SE-associated oncogenes was then detected by RNA-seq and further verified in 71 patients by real-time PCR.

RESULTS

SE associated with many new oncogenes in lung adenocarcinoma, among which, was up-regulated in A549 and 31 of 71 patients. High expression of could inhibit cell proliferation, indicating its potential as a new biomarker for lung adenocarcinoma.