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Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data

Background: Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or viral infections. Patients with FLC generally have non-specific symptoms, are often diagnosed at a later stage, and experience a higher frequenc...

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Autores principales: Kim, Janghyun, Kim, Young, Lee, Bora
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530820/
https://www.ncbi.nlm.nih.gov/pubmed/37761849
http://dx.doi.org/10.3390/genes14091709
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author Kim, Janghyun
Kim, Young
Lee, Bora
author_facet Kim, Janghyun
Kim, Young
Lee, Bora
author_sort Kim, Janghyun
collection PubMed
description Background: Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or viral infections. Patients with FLC generally have non-specific symptoms, are often diagnosed at a later stage, and experience a higher frequency of metastases compared to patients with other liver cancers. A fusion transcript of DNAJB1 and PRKACA, which can lead to increased activity of PKA and cellular proliferation, has been identified in all FLC patients, but the exact mechanism through which FLC develops remains unclear. In this study, we investigated common lncRNA profiles in various FLC samples using bioinformatics analyses. Methods: We analyzed differentially expressed (DE) lncRNAs from three RNA sequencing datasets. Using lncRNAs and DE mRNAs, we predicted potential lncRNA target genes and performed Gene Ontology (GO) and KEGG analyses with the DE lncRNA target genes. Moreover, we screened for small-molecule compounds that could act as therapeutic targets for FLC. Results: We identified 308 DE lncRNAs from the RNA sequencing datasets. In addition, we performed a trans-target prediction analysis and identified 454 co-expressed pairs in FLC. The GO analysis showed that the lncRNA-related up-regulated mRNAs were enriched in the regulation of protein kinase C signaling and cAMP catabolic processes, while lncRNA-related down-regulated mRNAs were enriched in steroid, retinol, cholesterol, and xenobiotic metabolic processes. The analysis of small-molecule compounds for FLC treatment identified vitexin, chlorthalidone, triamterene, and amiloride, among other compounds. Conclusions: We identified potential therapeutic targets for FLC, including lncRNA target genes as well as small-molecule compounds that could potentially be used as treatments. Our findings could contribute to furthering our understanding of FLC and providing potential avenues for diagnosis and treatment.
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spelling pubmed-105308202023-09-28 Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data Kim, Janghyun Kim, Young Lee, Bora Genes (Basel) Article Background: Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that primarily affects adolescents and young adults without prior liver disease or viral infections. Patients with FLC generally have non-specific symptoms, are often diagnosed at a later stage, and experience a higher frequency of metastases compared to patients with other liver cancers. A fusion transcript of DNAJB1 and PRKACA, which can lead to increased activity of PKA and cellular proliferation, has been identified in all FLC patients, but the exact mechanism through which FLC develops remains unclear. In this study, we investigated common lncRNA profiles in various FLC samples using bioinformatics analyses. Methods: We analyzed differentially expressed (DE) lncRNAs from three RNA sequencing datasets. Using lncRNAs and DE mRNAs, we predicted potential lncRNA target genes and performed Gene Ontology (GO) and KEGG analyses with the DE lncRNA target genes. Moreover, we screened for small-molecule compounds that could act as therapeutic targets for FLC. Results: We identified 308 DE lncRNAs from the RNA sequencing datasets. In addition, we performed a trans-target prediction analysis and identified 454 co-expressed pairs in FLC. The GO analysis showed that the lncRNA-related up-regulated mRNAs were enriched in the regulation of protein kinase C signaling and cAMP catabolic processes, while lncRNA-related down-regulated mRNAs were enriched in steroid, retinol, cholesterol, and xenobiotic metabolic processes. The analysis of small-molecule compounds for FLC treatment identified vitexin, chlorthalidone, triamterene, and amiloride, among other compounds. Conclusions: We identified potential therapeutic targets for FLC, including lncRNA target genes as well as small-molecule compounds that could potentially be used as treatments. Our findings could contribute to furthering our understanding of FLC and providing potential avenues for diagnosis and treatment. MDPI 2023-08-28 /pmc/articles/PMC10530820/ /pubmed/37761849 http://dx.doi.org/10.3390/genes14091709 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Janghyun
Kim, Young
Lee, Bora
Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data
title Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data
title_full Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data
title_fullStr Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data
title_full_unstemmed Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data
title_short Identification of Long Non-Coding RNA Profiles and Potential Therapeutic Agents for Fibrolamellar Carcinoma Based on RNA-Sequencing Data
title_sort identification of long non-coding rna profiles and potential therapeutic agents for fibrolamellar carcinoma based on rna-sequencing data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530820/
https://www.ncbi.nlm.nih.gov/pubmed/37761849
http://dx.doi.org/10.3390/genes14091709
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