Abstract
A growing number of long non-coding RNAs (lncRNAs) have been linked to squamous cell carcinoma of the head and neck (SCCHN). A subclass of lncRNAs, termed enhancer RNAs (eRNAs), are derived from enhancer regions and could contribute to enhancer function. In this study, we developed an integrated data analysis approach to identify key eRNAs in SCCHN. Tissue-specific enhancer-derived RNAs and their regulated genes previously predicted using the computational pipeline PreSTIGE, were considered as putative eRNA-target pairs. The interactive web servers, TANRIC (the Atlas of Noncoding RNAs in Cancer) and cBioPortal, were used to explore the RNA levels and clinical data from the Cancer Genome Atlas (TCGA) project. Requiring that key eRNAs should show significant associations with overall survival (Kaplan–Meier log-rank test, p < 0.05) and the predicted target (correlation coefficient r > 0.4, p < 0.001), we identified five key eRNA candidates. The most significant survival-associated eRNA was AP001056.1 with ICOSLG encoding an immune checkpoint protein as its regulated target. Another 1640 genes also showed significant correlation with AP001056.1 (r > 0.4, p < 0.001), with the “immune system process” being the most significantly enriched biological process (adjusted p < 0.001). Our results suggest that AP001056.1 is a key immune-related eRNA in SCCHN with a positive impact on clinical outcome.
Highlights
Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide with an estimated 600,000 new cases and 300,000 deaths annually [1]
Patients provided by the TANRIC database, we identified 18 of the 1288 putative enhancer RNAs (eRNAs) genes with levels significantly associated with overall survival (Table 1, Kaplan–Meier log-rank test, p < 0.05)
Discussion eRNAs are a specific subclass of long non-coding RNAs (lncRNAs) derived within gene enhancer regions and are able eRNAs areinfluence a specifictranscription subclass of lncRNAs derived within geneTo enhancer and are able to to act in cis to of the corresponding gene
Summary
Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide with an estimated 600,000 new cases and 300,000 deaths annually [1]. Human papillomavirus (HPV) infection are the most common predisposing factors for SCCHN [2,3]. Evidence is accumulating that long non-coding RNAs (lncRNAs) are linked to human diseases [4,5]. In contrast with the classic notion that non-protein-coding transcripts are non-functional and regarded as junk RNA, lncRNAs are biologically active and carry out diverse functions such as transcriptional regulation in cis or trans, the organization of nuclear domains and post-transcriptional regulation of proteins or RNA molecules [6,7]. Next-generation sequencing has identified tens of thousands of lncRNAs from single-cell eukaryotes to humans [8].
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