Super enhancer associated RAI14 is a new potential biomarker in lung adenocarcinoma.
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ABSTRACT: Purpose
Tyrosine kinase inhibitors (TKIs) are widely used to treat lung adenocarcinoma patients with EGFR mutations or ALK-fusions. However, patients with wild-type genes or TKIs-resistant mutations lack effective therapeutic targets. Extensive studies reveal that super enhancer (SE), a large cis-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, RAI14 was up-regulated in A549 and 31 of 71 patients. High expression of RAI14 could inhibit cell proliferation, indicating its potential as a new biomarker for lung adenocarcinoma.
SUBMITTER: Yuan C
PROVIDER: S-EPMC5739635 | biostudies-literature | 2017 Dec
REPOSITORIES: biostudies-literature
Publications
Super enhancer associated <i>RAI14</i> is a new potential biomarker in lung adenocarcinoma.
Yuan Chongze C Hu Hong H Kuang Muyu M Chen Zongwei Z Tao Xiaoting X Fang Shengjian S Sun Yihua Y Zhang Yawei Y Chen Haiquan H
Oncotarget 20171027 62
<h4>Purpose</h4>Tyrosine kinase inhibitors (TKIs) are widely used to treat lung adenocarcinoma patients with <i>EGFR</i> mutations or <i>ALK</i>-fusions. However, patients with wild-type genes or TKIs-resistant mutations lack effective therapeutic targets. Extensive studies reveal that super enhancer (SE), a large <i>cis</i>-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 wor ...[more]
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Project description:Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating 110 epigenomic profiles from primary GCs, normal gastric tissues and cell lines, we highlight 36,973 predicted enhancers and 3,759 predicted super-enhancers respectively. Cell-line-defined super-enhancers can be subclassified by their somatic alteration status into somatic gain, loss and unaltered categories, each displaying distinct epigenetic, transcriptional and pathway enrichments. Somatic gain super-enhancers are associated with complex chromatin interaction profiles, expression patterns correlated with patient outcome and dense co-occupancy of the transcription factors CDX2 and HNF4α. Somatic super-enhancers are also enriched in genetic risk SNPs associated with cancer predisposition. Our results reveal a genome-wide reprogramming of the GC enhancer and super-enhancer landscape during tumorigenesis, contributing to dysregulated local and regional cancer gene expression.
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