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LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network

BACKGROUND: It is becoming increasingly clear that cancers can rarely be ascribed to just one or a few genomic variations. Genes generally do not function alone, but in groups that function as “networks”. This study aimed to develop a competing endogenous RNA (ceRNA) network to elucidate the role of...

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Autores principales: Zhong, Min-Er, Chen, Yanyu, Zhang, Guannan, Xu, Lai, Ge, Wei, Wu, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543669/
https://www.ncbi.nlm.nih.gov/pubmed/31164794
http://dx.doi.org/10.1186/s12935-019-0866-2
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author Zhong, Min-Er
Chen, Yanyu
Zhang, Guannan
Xu, Lai
Ge, Wei
Wu, Bin
author_facet Zhong, Min-Er
Chen, Yanyu
Zhang, Guannan
Xu, Lai
Ge, Wei
Wu, Bin
author_sort Zhong, Min-Er
collection PubMed
description BACKGROUND: It is becoming increasingly clear that cancers can rarely be ascribed to just one or a few genomic variations. Genes generally do not function alone, but in groups that function as “networks”. This study aimed to develop a competing endogenous RNA (ceRNA) network to elucidate the role of long non-coding RNA H19 in colorectal cancer. METHODS: Large-scale RNA-seq data was obtained from The Cancer Genome Atlas database. Differentially expressed RNAs were identified by bioinformatics analysis, and a competing endogenous RNA network was constructed. Functional enrichment analysis and correlation analysis between competing endogenous RNAs and clinical features were performed to reveal their roles in the tumorigenesis of colorectal cancer. To verify the conclusions derived from bioinformatics analysis, we investigated the effect of lncRNA H19 knockdown in human colorectal cancer cell lines HT-29 and HCT116. RESULTS: The present study successfully identify various cancer-specific lncRNAs and pseudogenes in CRC. The lncRNA/pseudogene–miRNA–mRNA ceRNA network was constructed using 10 lncRNAs, 5 pseudogenes, 122 mRNAs and 39 miRNAs. In the ceRNA network of CRC, H19 up-regulates various cancer-related mRNA by competitively sponging various miRNA, and participates in PI3K–Akt signaling pathway in this manner. Cox regression and correlation analysis showed that H19 and some other competing endogenous RNAs in the network are associated with poor prognosis and clinical parameters such as tumor grade and metastasis. Knockdown of H19 reduces the protein level of MET, ZEB1, and COL1A1 in vitro. CONCLUSIONS: H19 regulates PI3K–Akt signal pathway through a competing endogenous RNA network and predicts poor prognosis in colorectal cancer. The pseudogene RPLP0P2 may be an important oncogene like H19 and needs to be studied further. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0866-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-65436692019-06-04 LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network Zhong, Min-Er Chen, Yanyu Zhang, Guannan Xu, Lai Ge, Wei Wu, Bin Cancer Cell Int Primary Research BACKGROUND: It is becoming increasingly clear that cancers can rarely be ascribed to just one or a few genomic variations. Genes generally do not function alone, but in groups that function as “networks”. This study aimed to develop a competing endogenous RNA (ceRNA) network to elucidate the role of long non-coding RNA H19 in colorectal cancer. METHODS: Large-scale RNA-seq data was obtained from The Cancer Genome Atlas database. Differentially expressed RNAs were identified by bioinformatics analysis, and a competing endogenous RNA network was constructed. Functional enrichment analysis and correlation analysis between competing endogenous RNAs and clinical features were performed to reveal their roles in the tumorigenesis of colorectal cancer. To verify the conclusions derived from bioinformatics analysis, we investigated the effect of lncRNA H19 knockdown in human colorectal cancer cell lines HT-29 and HCT116. RESULTS: The present study successfully identify various cancer-specific lncRNAs and pseudogenes in CRC. The lncRNA/pseudogene–miRNA–mRNA ceRNA network was constructed using 10 lncRNAs, 5 pseudogenes, 122 mRNAs and 39 miRNAs. In the ceRNA network of CRC, H19 up-regulates various cancer-related mRNA by competitively sponging various miRNA, and participates in PI3K–Akt signaling pathway in this manner. Cox regression and correlation analysis showed that H19 and some other competing endogenous RNAs in the network are associated with poor prognosis and clinical parameters such as tumor grade and metastasis. Knockdown of H19 reduces the protein level of MET, ZEB1, and COL1A1 in vitro. CONCLUSIONS: H19 regulates PI3K–Akt signal pathway through a competing endogenous RNA network and predicts poor prognosis in colorectal cancer. The pseudogene RPLP0P2 may be an important oncogene like H19 and needs to be studied further. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12935-019-0866-2) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-30 /pmc/articles/PMC6543669/ /pubmed/31164794 http://dx.doi.org/10.1186/s12935-019-0866-2 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Zhong, Min-Er
Chen, Yanyu
Zhang, Guannan
Xu, Lai
Ge, Wei
Wu, Bin
LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
title LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
title_full LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
title_fullStr LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
title_full_unstemmed LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
title_short LncRNA H19 regulates PI3K–Akt signal pathway by functioning as a ceRNA and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncRNA-associated ceRNA network
title_sort lncrna h19 regulates pi3k–akt signal pathway by functioning as a cerna and predicts poor prognosis in colorectal cancer: integrative analysis of dysregulated ncrna-associated cerna network
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6543669/
https://www.ncbi.nlm.nih.gov/pubmed/31164794
http://dx.doi.org/10.1186/s12935-019-0866-2
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