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MicroRNA profile in HBV-induced infection and hepatocellular carcinoma

BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for mak...

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Autores principales: Wang, Guanyu, Dong, Fulu, Xu, Zhiyao, Sharma, Sherven, Hu, Xiaotong, Chen, Dafang, Zhang, Lumin, Zhang, Jinping, Dong, Qinghua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709924/
https://www.ncbi.nlm.nih.gov/pubmed/29191172
http://dx.doi.org/10.1186/s12885-017-3816-1
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author Wang, Guanyu
Dong, Fulu
Xu, Zhiyao
Sharma, Sherven
Hu, Xiaotong
Chen, Dafang
Zhang, Lumin
Zhang, Jinping
Dong, Qinghua
author_facet Wang, Guanyu
Dong, Fulu
Xu, Zhiyao
Sharma, Sherven
Hu, Xiaotong
Chen, Dafang
Zhang, Lumin
Zhang, Jinping
Dong, Qinghua
author_sort Wang, Guanyu
collection PubMed
description BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. METHODS: To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection. CONCLUSION: Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3816-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-57099242017-12-06 MicroRNA profile in HBV-induced infection and hepatocellular carcinoma Wang, Guanyu Dong, Fulu Xu, Zhiyao Sharma, Sherven Hu, Xiaotong Chen, Dafang Zhang, Lumin Zhang, Jinping Dong, Qinghua BMC Cancer Research Article BACKGROUND: MicroRNAs (miRNAs) exhibit essential regulatory functions related to cell growth, apoptosis, development and differentiation. Dysregulated expression of miRNAs is associated with a wide variety of human diseases. As such miRNA signatures are valuable as biomarkers for disease and for making treatment decisions. Hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma (HCC). Here we screened for miRNAs in chronic HBV associated HCC. METHODS: To determine the miRNAs in HCC occurrence associated with HBV infection, we analyzed global miRNA expression profiles in 12 pairs of HCC and adjacent matched non-HCC tissues from HBV-positive and HBV-negative patients using microarray analyses. The microarray result was validated by real-time PCR in 32 HBV-positive and 24 HBV-negative patient HCC samples. The potential candidate target genes of the miRNAs were predicted by miRWalk software. Genes simultaneously predicted as targets by two or more miRNAs were subjected to GO and KEGG pathway analysis. The miRNA regulatory network analysis was performed using the Ingenuity Pathway Analysis (IPA) software. RESULTS: Eight miRNAs (miR-223, miR-98, miR-15b, miR-199a-5p, miR-19b, miR-22, miR-451, and miR-101) were involved in HBV-unrelated HCC, 5 miRNAs (miR-98, miR-375, miR-335, miR-199a-5p, and miR-22) were involved in HBV infection, and 7 miRNAs (miR-150, miR-342-3p, miR-663, miR-20b, miR-92a-3p, miR-376c-3p and miR-92b) were specifically altered in HBV-related HCC. Gene Ontology and KEGG analyses predict that these HBV-related HCC miRNAs are involved in the regulation of: transcription, RNA polymerase II promoter, phosphorylation of proteins through MAPK signaling pathway, focal adhesion, and actin cytoskeleton. IPA analysis also suggest that these miRNAs act on AGO2, TP53, CCND1, and 11 other genes that significantly influence HCC occurrence and HBV infection. CONCLUSION: Our data indicates that the unique 7 miRNAs expression signature could be involved in the development HBV- related HCC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-017-3816-1) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-01 /pmc/articles/PMC5709924/ /pubmed/29191172 http://dx.doi.org/10.1186/s12885-017-3816-1 Text en © The Author(s). 2017 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 Research Article
Wang, Guanyu
Dong, Fulu
Xu, Zhiyao
Sharma, Sherven
Hu, Xiaotong
Chen, Dafang
Zhang, Lumin
Zhang, Jinping
Dong, Qinghua
MicroRNA profile in HBV-induced infection and hepatocellular carcinoma
title MicroRNA profile in HBV-induced infection and hepatocellular carcinoma
title_full MicroRNA profile in HBV-induced infection and hepatocellular carcinoma
title_fullStr MicroRNA profile in HBV-induced infection and hepatocellular carcinoma
title_full_unstemmed MicroRNA profile in HBV-induced infection and hepatocellular carcinoma
title_short MicroRNA profile in HBV-induced infection and hepatocellular carcinoma
title_sort microrna profile in hbv-induced infection and hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709924/
https://www.ncbi.nlm.nih.gov/pubmed/29191172
http://dx.doi.org/10.1186/s12885-017-3816-1
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