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CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma
To explore and understand the competitive mechanism of ceRNAs in intrahepatic cholangiocarcinoma (ICC), we used bioinformatics analysis methods to construct an ICC-related ceRNA regulatory network (ceRNET), which contained 340 lncRNA-miRNA-mRNA regulatory relationships based on the RNA expression da...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053603/ https://www.ncbi.nlm.nih.gov/pubmed/31956102 http://dx.doi.org/10.18632/aging.102634 |
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author | Xu, Weiyu Yu, Si Xiong, Jianping Long, Junyu Zheng, Yongchang Sang, Xinting |
author_facet | Xu, Weiyu Yu, Si Xiong, Jianping Long, Junyu Zheng, Yongchang Sang, Xinting |
author_sort | Xu, Weiyu |
collection | PubMed |
description | To explore and understand the competitive mechanism of ceRNAs in intrahepatic cholangiocarcinoma (ICC), we used bioinformatics analysis methods to construct an ICC-related ceRNA regulatory network (ceRNET), which contained 340 lncRNA-miRNA-mRNA regulatory relationships based on the RNA expression datasets in the NCBI GEO database. We identified the core regulatory pathway RP11-328K4.1-hsa-miR-27a-3p-PROS1, which is related to ICC, for further validation by molecular biology assays. GO analysis of 44 differentially expressed mRNAs in ceRNET revealed that they were mainly enriched in biological processes including “negative regulation of epithelial cell proliferation” and "positive regulation of activated T lymphocyte proliferation.” KEGG analysis showed that they were mainly enriched in the “complement and coagulation cascade” pathway. The molecular biology assay showed that lncRNA RP11-328K4.1 expression was significantly lower in the cancerous tissues and peripheral plasma of ICC patients than in normal controls (p<0.05). In addition, hsa-miR-27a-3p was found to be significantly upregulated in the cancer tissues and peripheral plasma of ICC patients (p<0.05). Compared to normal controls, the expression of PROS1 mRNA was significantly downregulated in ICC patient cancer tissues (p<0.05) but not in peripheral plasma (p>0.05). Furthermore, ROC analysis revealed that RP11-328K4.1, hsa-miR-27a-3p, and PROS1 had significant diagnostic value in ICC. We concluded that the upregulation of lncRNA RP11-328K4.1, which might act as a miRNA sponge, exerts an antitumor effect in ICC by eliminating the inhibition of PROS1 mRNA expression by oncogenic miRNA hsa-miR-27a. |
format | Online Article Text |
id | pubmed-7053603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-70536032020-03-12 CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma Xu, Weiyu Yu, Si Xiong, Jianping Long, Junyu Zheng, Yongchang Sang, Xinting Aging (Albany NY) Research Paper To explore and understand the competitive mechanism of ceRNAs in intrahepatic cholangiocarcinoma (ICC), we used bioinformatics analysis methods to construct an ICC-related ceRNA regulatory network (ceRNET), which contained 340 lncRNA-miRNA-mRNA regulatory relationships based on the RNA expression datasets in the NCBI GEO database. We identified the core regulatory pathway RP11-328K4.1-hsa-miR-27a-3p-PROS1, which is related to ICC, for further validation by molecular biology assays. GO analysis of 44 differentially expressed mRNAs in ceRNET revealed that they were mainly enriched in biological processes including “negative regulation of epithelial cell proliferation” and "positive regulation of activated T lymphocyte proliferation.” KEGG analysis showed that they were mainly enriched in the “complement and coagulation cascade” pathway. The molecular biology assay showed that lncRNA RP11-328K4.1 expression was significantly lower in the cancerous tissues and peripheral plasma of ICC patients than in normal controls (p<0.05). In addition, hsa-miR-27a-3p was found to be significantly upregulated in the cancer tissues and peripheral plasma of ICC patients (p<0.05). Compared to normal controls, the expression of PROS1 mRNA was significantly downregulated in ICC patient cancer tissues (p<0.05) but not in peripheral plasma (p>0.05). Furthermore, ROC analysis revealed that RP11-328K4.1, hsa-miR-27a-3p, and PROS1 had significant diagnostic value in ICC. We concluded that the upregulation of lncRNA RP11-328K4.1, which might act as a miRNA sponge, exerts an antitumor effect in ICC by eliminating the inhibition of PROS1 mRNA expression by oncogenic miRNA hsa-miR-27a. Impact Journals 2020-01-19 /pmc/articles/PMC7053603/ /pubmed/31956102 http://dx.doi.org/10.18632/aging.102634 Text en Copyright © 2020 Xu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Xu, Weiyu Yu, Si Xiong, Jianping Long, Junyu Zheng, Yongchang Sang, Xinting CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma |
title | CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma |
title_full | CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma |
title_fullStr | CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma |
title_full_unstemmed | CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma |
title_short | CeRNA regulatory network-based analysis to study the roles of noncoding RNAs in the pathogenesis of intrahepatic cholangiocellular carcinoma |
title_sort | cerna regulatory network-based analysis to study the roles of noncoding rnas in the pathogenesis of intrahepatic cholangiocellular carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053603/ https://www.ncbi.nlm.nih.gov/pubmed/31956102 http://dx.doi.org/10.18632/aging.102634 |
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