Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes

Smoking and HPV infection are known causes for the vast majority of head and neck squamous cell carcinomas (HNSCC) due to their likelihood of causing gene dysregulation and genomic alterations. Enhancer RNAs (eRNAs) are non-coding RNAs that are known to increase nearby and target gene expression, an...

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Autores principales:	Neil Shende, Jingyue Xu, Wei Tse Li, Jeffrey Liu, Jaideep Chakladar, Kevin T. Brumund, Weg M. Ongkeko
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	HNSCC eRNA smoking HPV Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1e042b4898d9475db65cbe9e0a1c03c9
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spelling	oai:doaj.org-article:1e042b4898d9475db65cbe9e0a1c03c92021-11-25T17:57:41ZEnhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes10.3390/ijms2222125461422-00671661-6596https://doaj.org/article/1e042b4898d9475db65cbe9e0a1c03c92021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12546https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Smoking and HPV infection are known causes for the vast majority of head and neck squamous cell carcinomas (HNSCC) due to their likelihood of causing gene dysregulation and genomic alterations. Enhancer RNAs (eRNAs) are non-coding RNAs that are known to increase nearby and target gene expression, and activity that has been suggested to be affected by genetic and epigenetic alterations. Here we sought to identify the effects of smoking and HPV status on eRNA expression in HNSCC tumors. We focused on four patient cohorts including smoking/HPV+, smoking/HPV−, non-smoking/HPV+, and non-smoking/HPV− patients. We used TCGA RNA-seq data from cancer tumors and adjacent normal tissue, extracted eRNA read counts, and correlated these to survival, clinical variables, immune infiltration, cancer pathways, and genomic alterations. We found a large number of differentially expressed eRNA in each patient cohort. We also found several dysregulated eRNA correlated to patient survival, clinical variables, immune pathways, and genomic alterations. Additionally, we were able to find dysregulated eRNA nearby seven key HNSCC-related oncogenes. For example, we found eRNA chr14:103272042–103272430 (eRNA-24036), which is located close to the TRAF3 gene to be differentially expressed and correlated with the pathologic N stage and immune cell populations. Using a separate validation dataset, we performed differential expression and immune infiltration analysis to validate our results from the TCGA data. Our findings may explain the association between eRNA expression, enhancer activity, and nearby gene dysregulation.Neil ShendeJingyue XuWei Tse LiJeffrey LiuJaideep ChakladarKevin T. BrumundWeg M. OngkekoMDPI AGarticleHNSCCeRNAsmokingHPVBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12546, p 12546 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	HNSCC eRNA smoking HPV Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	HNSCC eRNA smoking HPV Biology (General) QH301-705.5 Chemistry QD1-999 Neil Shende Jingyue Xu Wei Tse Li Jeffrey Liu Jaideep Chakladar Kevin T. Brumund Weg M. Ongkeko Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
description	Smoking and HPV infection are known causes for the vast majority of head and neck squamous cell carcinomas (HNSCC) due to their likelihood of causing gene dysregulation and genomic alterations. Enhancer RNAs (eRNAs) are non-coding RNAs that are known to increase nearby and target gene expression, and activity that has been suggested to be affected by genetic and epigenetic alterations. Here we sought to identify the effects of smoking and HPV status on eRNA expression in HNSCC tumors. We focused on four patient cohorts including smoking/HPV+, smoking/HPV−, non-smoking/HPV+, and non-smoking/HPV− patients. We used TCGA RNA-seq data from cancer tumors and adjacent normal tissue, extracted eRNA read counts, and correlated these to survival, clinical variables, immune infiltration, cancer pathways, and genomic alterations. We found a large number of differentially expressed eRNA in each patient cohort. We also found several dysregulated eRNA correlated to patient survival, clinical variables, immune pathways, and genomic alterations. Additionally, we were able to find dysregulated eRNA nearby seven key HNSCC-related oncogenes. For example, we found eRNA chr14:103272042–103272430 (eRNA-24036), which is located close to the TRAF3 gene to be differentially expressed and correlated with the pathologic N stage and immune cell populations. Using a separate validation dataset, we performed differential expression and immune infiltration analysis to validate our results from the TCGA data. Our findings may explain the association between eRNA expression, enhancer activity, and nearby gene dysregulation.
format	article
author	Neil Shende Jingyue Xu Wei Tse Li Jeffrey Liu Jaideep Chakladar Kevin T. Brumund Weg M. Ongkeko
author_facet	Neil Shende Jingyue Xu Wei Tse Li Jeffrey Liu Jaideep Chakladar Kevin T. Brumund Weg M. Ongkeko
author_sort	Neil Shende
title	Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
title_short	Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
title_full	Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
title_fullStr	Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
title_full_unstemmed	Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes
title_sort	enhancer rna profiling in smoking and hpv associated hnscc reveals associations to key oncogenes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1e042b4898d9475db65cbe9e0a1c03c9
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Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes

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