Super enhancer associated RAI14 is a new potential biomarker in lung adenocarcinoma
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Chongze Yuan1,2,*, Hong Hu1,2,*, Muyu Kuang1,2,*, Zongwei Chen4, Xiaoting Tao1,2, Shengjian Fang1,2, Yihua Sun1,2, Yawei Zhang1,2 and Haiquan Chen1,2,3
1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
3Institutes of Biomedical Sciences, Fudan University, Shanghai, China
4Department of Thoracic Surgery, Zhongshan Hospital, Shanghai, China
*These authors have contributed equally to this work
Yihua Sun, email: [email protected]
Yawei Zhang, email: [email protected]
Haiquan Chen, email: [email protected]
Keywords: lung cancer; ChIP-seq; super enhancer; RAI14; targeted therapy
Abbreviations: SE: super enhancer; TE: typical enhancer; TKIs: tyrosine kinase inhibitors; ChIP-seq: Chromatin Immunoprecipitation followed by high-throughput DNA sequencing; NSCLC: non-small cell lung cancer
Received: December 23, 2016 Accepted: September 23, 2017 Published: October 27, 2017
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.
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