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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
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.
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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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