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Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC
Long noncoding RNAs (lncRNAs) have important regulatory roles in cancer biology. Although some lncRNAs have well‐characterized functions, the vast majority of this class of molecules remains functionally uncharacterized. To systematically pinpoint functional lncRNAs, a computational approach was pro...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463357/ https://www.ncbi.nlm.nih.gov/pubmed/32460441 http://dx.doi.org/10.1002/1878-0261.12726 |
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author | Wang, Qiu‐Yu Peng, Liu Chen, Yang Liao, Lian‐Di Chen, Jia‐Xin Li, Meng Li, Yan‐Yu Qian, Feng‐Cui Zhang, Yue‐Xin Wang, Fan Li, Chun‐Quan Lin, De‐Chen Xu, Li‐Yan Li, En‐Min |
author_facet | Wang, Qiu‐Yu Peng, Liu Chen, Yang Liao, Lian‐Di Chen, Jia‐Xin Li, Meng Li, Yan‐Yu Qian, Feng‐Cui Zhang, Yue‐Xin Wang, Fan Li, Chun‐Quan Lin, De‐Chen Xu, Li‐Yan Li, En‐Min |
author_sort | Wang, Qiu‐Yu |
collection | PubMed |
description | Long noncoding RNAs (lncRNAs) have important regulatory roles in cancer biology. Although some lncRNAs have well‐characterized functions, the vast majority of this class of molecules remains functionally uncharacterized. To systematically pinpoint functional lncRNAs, a computational approach was proposed for identification of lncRNA‐mediated competing endogenous RNAs (ceRNAs) through combining global and local regulatory direction consistency of expression. Using esophageal squamous cell carcinoma (ESCC) as model, we further identified many known and novel functional lncRNAs acting as ceRNAs (ce‐lncRNAs). We found that most of them significantly regulated the expression of cancer‐related hallmark genes. These ce‐lncRNAs were significantly regulated by enhancers, especially super‐enhancers (SEs). Landscape analyses for lncRNAs further identified SE‐associated functional ce‐lncRNAs in ESCC, such as HOTAIR, XIST, SNHG5, and LINC00094. THZ1, a specific CDK7 inhibitor, can result in global transcriptional downregulation of SE‐associated ce‐lncRNAs. We further demonstrate that a SE‐associated ce‐lncRNA, LINC00094 can be activated by transcription factors TCF3 and KLF5 through binding to SE regions and promoted ESCC cancer cell growth. THZ1 downregulated expression of LINC00094 through inhibiting TCF3 and KLF5. Our data demonstrated the important roles of SE‐associated ce‐lncRNAs in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy. |
format | Online Article Text |
id | pubmed-7463357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74633572020-09-08 Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC Wang, Qiu‐Yu Peng, Liu Chen, Yang Liao, Lian‐Di Chen, Jia‐Xin Li, Meng Li, Yan‐Yu Qian, Feng‐Cui Zhang, Yue‐Xin Wang, Fan Li, Chun‐Quan Lin, De‐Chen Xu, Li‐Yan Li, En‐Min Mol Oncol Research Articles Long noncoding RNAs (lncRNAs) have important regulatory roles in cancer biology. Although some lncRNAs have well‐characterized functions, the vast majority of this class of molecules remains functionally uncharacterized. To systematically pinpoint functional lncRNAs, a computational approach was proposed for identification of lncRNA‐mediated competing endogenous RNAs (ceRNAs) through combining global and local regulatory direction consistency of expression. Using esophageal squamous cell carcinoma (ESCC) as model, we further identified many known and novel functional lncRNAs acting as ceRNAs (ce‐lncRNAs). We found that most of them significantly regulated the expression of cancer‐related hallmark genes. These ce‐lncRNAs were significantly regulated by enhancers, especially super‐enhancers (SEs). Landscape analyses for lncRNAs further identified SE‐associated functional ce‐lncRNAs in ESCC, such as HOTAIR, XIST, SNHG5, and LINC00094. THZ1, a specific CDK7 inhibitor, can result in global transcriptional downregulation of SE‐associated ce‐lncRNAs. We further demonstrate that a SE‐associated ce‐lncRNA, LINC00094 can be activated by transcription factors TCF3 and KLF5 through binding to SE regions and promoted ESCC cancer cell growth. THZ1 downregulated expression of LINC00094 through inhibiting TCF3 and KLF5. Our data demonstrated the important roles of SE‐associated ce‐lncRNAs in ESCC oncogenesis and might serve as targets for ESCC diagnosis and therapy. John Wiley and Sons Inc. 2020-06-20 2020-09 /pmc/articles/PMC7463357/ /pubmed/32460441 http://dx.doi.org/10.1002/1878-0261.12726 Text en © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Wang, Qiu‐Yu Peng, Liu Chen, Yang Liao, Lian‐Di Chen, Jia‐Xin Li, Meng Li, Yan‐Yu Qian, Feng‐Cui Zhang, Yue‐Xin Wang, Fan Li, Chun‐Quan Lin, De‐Chen Xu, Li‐Yan Li, En‐Min Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC |
title | Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC |
title_full | Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC |
title_fullStr | Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC |
title_full_unstemmed | Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC |
title_short | Characterization of super‐enhancer‐associated functional lncRNAs acting as ceRNAs in ESCC |
title_sort | characterization of super‐enhancer‐associated functional lncrnas acting as cernas in escc |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463357/ https://www.ncbi.nlm.nih.gov/pubmed/32460441 http://dx.doi.org/10.1002/1878-0261.12726 |
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