Bioinformatics approach to predict target genes for dysregulated microRNAs in hepatocellular carcinoma: study on a chemically-induced HCC mouse model

Hepatocellular carcinoma (HCC) is an aggressive epithelial tumor which shows very poor prognosis and high rate of recurrence, representing an urgent problem for public healthcare. MicroRNAs (miRNAs/miRs) are a class of small, non-coding RNAs that attract great attention because of their role in regu...

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Veröffentlicht in:BMC bioinformatics 2015-12, Vol.16 (1), p.408-408, Article 408
Hauptverfasser: Del Vecchio, Filippo, Gallo, Francesco, Di Marco, Antinisca, Mastroiaco, Valentina, Caianiello, Pasquale, Zazzeroni, Francesca, Alesse, Edoardo, Tessitore, Alessandra
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container_issue 1
container_start_page 408
container_title BMC bioinformatics
container_volume 16
creator Del Vecchio, Filippo
Gallo, Francesco
Di Marco, Antinisca
Mastroiaco, Valentina
Caianiello, Pasquale
Zazzeroni, Francesca
Alesse, Edoardo
Tessitore, Alessandra
description Hepatocellular carcinoma (HCC) is an aggressive epithelial tumor which shows very poor prognosis and high rate of recurrence, representing an urgent problem for public healthcare. MicroRNAs (miRNAs/miRs) are a class of small, non-coding RNAs that attract great attention because of their role in regulation of processes such as cellular growth, proliferation, apoptosis. Because of the thousands of potential interactions between a single miR and target mRNAs, bioinformatics prediction tools are very useful to facilitate the task for individuating and selecting putative target genes. In this study, we present a chemically-induced HCC mouse model to identify differential expression of miRNAs during the progression of the hepatic injury up to HCC onset. In addition, we describe an established bioinformatics approach to highlight putative target genes and protein interaction networks where they are involved. We describe four miRs (miR-125a-5p, miR-27a, miR-182, miR-193b) which showed to be differentially expressed in the chemically-induced HCC mouse model. The miRs were subjected to four of the most used predictions tools and 15 predicted target genes were identified. The expression of one (ANK3) among the 15 predicted targets was further validated by immunoblotting. Then, enrichment annotation analysis was performed revealing significant clusters, including some playing a role in ion transporter activity, regulation of receptor protein serine/threonine kinase signaling pathway, protein import into nucleus, regulation of intracellular protein transport, regulation of cell adhesion, growth factor binding, and regulation of TGF-beta/SMAD signaling pathway. A network construction was created and links between the selected miRs, the predicted targets as well as the possible interactions among them and other proteins were built up. In this study, we combined miRNA expression analysis, obtained by an in vivo HCC mouse model, with a bioinformatics-based workflow. New genes, pathways and protein interactions, putatively involved in HCC initiation and progression, were identified and explored.
doi_str_mv 10.1186/s12859-015-0836-1
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The expression of one (ANK3) among the 15 predicted targets was further validated by immunoblotting. Then, enrichment annotation analysis was performed revealing significant clusters, including some playing a role in ion transporter activity, regulation of receptor protein serine/threonine kinase signaling pathway, protein import into nucleus, regulation of intracellular protein transport, regulation of cell adhesion, growth factor binding, and regulation of TGF-beta/SMAD signaling pathway. A network construction was created and links between the selected miRs, the predicted targets as well as the possible interactions among them and other proteins were built up. In this study, we combined miRNA expression analysis, obtained by an in vivo HCC mouse model, with a bioinformatics-based workflow. 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subjects Analysis
Animals
Apoptosis
Cancer
Carcinoma, Hepatocellular - genetics
Computational biology
Computational Biology - methods
Gene Regulatory Networks
Genes
Genetic aspects
Hepatoma
Liver Neoplasms - genetics
Mice
Mice, Inbred C57BL
MicroRNA
MicroRNAs - genetics
Protein Interaction Maps
RNA, Messenger - genetics
RNA, Messenger - metabolism
Transforming growth factors
title Bioinformatics approach to predict target genes for dysregulated microRNAs in hepatocellular carcinoma: study on a chemically-induced HCC mouse model
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