Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study

BACKGROUND: Pediatric hepatocellular carcinoma (HCC) is a group of liver cancers whose mechanisms behind their pathogenesis and progression are poorly understood. AIM: We aimed to identify alterations in the expression of miRNAs and their putative target mRNAs in not only tumor tissues of patients w...

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Autores principales: Whyte, Senyo S., Karns, Rebekah, Min, Kyung‐Won, Cho, Jung‐Hyun, Lee, Sanghoon, Lake, Charissa, Bondoc, Alexander, Yoon, Je‐Hyun, Shin, Soona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875636/
https://www.ncbi.nlm.nih.gov/pubmed/35859536
http://dx.doi.org/10.1002/cnr2.1685
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author Whyte, Senyo S.
Karns, Rebekah
Min, Kyung‐Won
Cho, Jung‐Hyun
Lee, Sanghoon
Lake, Charissa
Bondoc, Alexander
Yoon, Je‐Hyun
Shin, Soona
author_facet Whyte, Senyo S.
Karns, Rebekah
Min, Kyung‐Won
Cho, Jung‐Hyun
Lee, Sanghoon
Lake, Charissa
Bondoc, Alexander
Yoon, Je‐Hyun
Shin, Soona
author_sort Whyte, Senyo S.
collection PubMed
description BACKGROUND: Pediatric hepatocellular carcinoma (HCC) is a group of liver cancers whose mechanisms behind their pathogenesis and progression are poorly understood. AIM: We aimed to identify alterations in the expression of miRNAs and their putative target mRNAs in not only tumor tissues of patients with pediatric HCC but also in corresponding non‐tumorous background livers by using liver tissues without underlying liver disease as a control. METHODS AND RESULTS: We performed a small‐scale miRNA and mRNA profiling of pediatric HCC (consisting of fibrolamellar carcinoma [FLC] and non‐FLC HCC) and paired liver tissues to identify miRNAs whose expression levels differed significantly from control livers without underlying liver disease. ToppMiR was used to prioritize both miRNAs and their putative target mRNAs in a gene‐annotation network, and the mRNA profile was used to refine the prioritization. Our analysis generated prioritized lists of miRNAs and mRNAs from the following three sets of analyses: (a) pediatric HCC versus control; (b) FLC versus control; and (c) corresponding non‐tumorous background liver tissues from the same patients with pediatric HCC versus control. No liver disease liver tissues were used as the control group for all analyses. Many miRNAs whose expressions were deregulated in pediatric HCC were consistent with their roles in adult HCC and/or other non‐hepatic cancers. Our gene ontology analysis of target mRNAs revealed enrichment of biological processes related to the sustenance and propagation of cancer and significant downregulation of metabolic processes. CONCLUSION: Our pilot study indicates that alterations in miRNA–mRNA networks were detected in not only tumor tissues but also corresponding non‐tumorous liver tissues from patients with pediatric HCC, suggesting multi‐faceted roles of miRNAs in disease progression. Our results may lead to novel hypotheses for future large‐scale studies.
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spelling pubmed-98756362023-01-25 Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study Whyte, Senyo S. Karns, Rebekah Min, Kyung‐Won Cho, Jung‐Hyun Lee, Sanghoon Lake, Charissa Bondoc, Alexander Yoon, Je‐Hyun Shin, Soona Cancer Rep (Hoboken) Original Articles BACKGROUND: Pediatric hepatocellular carcinoma (HCC) is a group of liver cancers whose mechanisms behind their pathogenesis and progression are poorly understood. AIM: We aimed to identify alterations in the expression of miRNAs and their putative target mRNAs in not only tumor tissues of patients with pediatric HCC but also in corresponding non‐tumorous background livers by using liver tissues without underlying liver disease as a control. METHODS AND RESULTS: We performed a small‐scale miRNA and mRNA profiling of pediatric HCC (consisting of fibrolamellar carcinoma [FLC] and non‐FLC HCC) and paired liver tissues to identify miRNAs whose expression levels differed significantly from control livers without underlying liver disease. ToppMiR was used to prioritize both miRNAs and their putative target mRNAs in a gene‐annotation network, and the mRNA profile was used to refine the prioritization. Our analysis generated prioritized lists of miRNAs and mRNAs from the following three sets of analyses: (a) pediatric HCC versus control; (b) FLC versus control; and (c) corresponding non‐tumorous background liver tissues from the same patients with pediatric HCC versus control. No liver disease liver tissues were used as the control group for all analyses. Many miRNAs whose expressions were deregulated in pediatric HCC were consistent with their roles in adult HCC and/or other non‐hepatic cancers. Our gene ontology analysis of target mRNAs revealed enrichment of biological processes related to the sustenance and propagation of cancer and significant downregulation of metabolic processes. CONCLUSION: Our pilot study indicates that alterations in miRNA–mRNA networks were detected in not only tumor tissues but also corresponding non‐tumorous liver tissues from patients with pediatric HCC, suggesting multi‐faceted roles of miRNAs in disease progression. Our results may lead to novel hypotheses for future large‐scale studies. John Wiley and Sons Inc. 2022-07-20 /pmc/articles/PMC9875636/ /pubmed/35859536 http://dx.doi.org/10.1002/cnr2.1685 Text en © 2022 The Authors. Cancer Reports published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Whyte, Senyo S.
Karns, Rebekah
Min, Kyung‐Won
Cho, Jung‐Hyun
Lee, Sanghoon
Lake, Charissa
Bondoc, Alexander
Yoon, Je‐Hyun
Shin, Soona
Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study
title Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study
title_full Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study
title_fullStr Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study
title_full_unstemmed Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study
title_short Integrated analysis using ToppMiR uncovers altered miRNA– mRNA regulatory networks in pediatric hepatocellular carcinoma—A pilot study
title_sort integrated analysis using toppmir uncovers altered mirna– mrna regulatory networks in pediatric hepatocellular carcinoma—a pilot study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875636/
https://www.ncbi.nlm.nih.gov/pubmed/35859536
http://dx.doi.org/10.1002/cnr2.1685
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