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Super enhancer associated RAI14 is a new potential biomarker in lung adenocarcinoma
Chongze Yuan1,2, Hong Hu1,2, Muyu Kuang1,2
1Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
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.
Insights
Super enhancers (SE) are linked to oncogenes in lung adenocarcinoma. This study identified RAI14 as a potential new biomarker, as its high expression inhibited cell proliferation in patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Tyrosine kinase inhibitors (TKIs) are standard treatments for lung adenocarcinoma with specific genetic mutations.
- Patients with wild-type genes or TKI-resistant mutations require novel therapeutic strategies.
- Super enhancers (SEs) are large regulatory elements implicated in oncogene activation across various cancers.
Purpose of the Study:
- To investigate the role of SEs in lung adenocarcinoma.
- To identify novel oncogenes and potential therapeutic targets by analyzing SE distribution.
- To discover new biomarkers for lung adenocarcinoma.
Main Methods:
- Chromatin Immunoprecipitation sequencing (ChIP-seq) for H3K27ac in lung adenocarcinoma cell lines.
- Comparative analysis of SE distribution between cancer cell lines and normal lung fibroblasts.
- RNA sequencing (RNA-seq) and real-time PCR to validate oncogene expression in patient samples.
Main Results:
- SEs were found to be associated with numerous novel oncogenes in lung adenocarcinoma.
- The gene RAI14 was identified as being upregulated in a subset of lung adenocarcinoma cell lines and patient tumors.
- Elevated RAI14 expression demonstrated an inhibitory effect on cancer cell proliferation.
Conclusions:
- RAI14 emerges as a potential novel biomarker for lung adenocarcinoma.
- Targeting SE-associated oncogenes represents a promising therapeutic avenue for lung adenocarcinoma.
- Further research into RAI14's role could lead to new treatment strategies.
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