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Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin

Metformin is a kind of widely used antidiabetic drug that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Recently, some studies showed that metformin exhibits anticancer properties in a variety of cancers. Although several antitumor mechani...

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Autores principales: Li, Chun-Qing, Liu, Zhi-Qin, Liu, Sha-Sha, Zhang, Gao-Tao, Jiang, Li, Chen, Chuan, Luo, Du-Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985428/
https://www.ncbi.nlm.nih.gov/pubmed/35401213
http://dx.doi.org/10.3389/fphar.2022.822023
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author Li, Chun-Qing
Liu, Zhi-Qin
Liu, Sha-Sha
Zhang, Gao-Tao
Jiang, Li
Chen, Chuan
Luo, Du-Qiang
author_facet Li, Chun-Qing
Liu, Zhi-Qin
Liu, Sha-Sha
Zhang, Gao-Tao
Jiang, Li
Chen, Chuan
Luo, Du-Qiang
author_sort Li, Chun-Qing
collection PubMed
description Metformin is a kind of widely used antidiabetic drug that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Recently, some studies showed that metformin exhibits anticancer properties in a variety of cancers. Although several antitumor mechanisms have been proposed for metformin action, its mode of action in human liver cancer remains not elucidated. In our study, we investigated the underlying molecular mechanisms of metformin's antitumor effect on Huh-7 cells of hepatocellular carcinoma (HCC) in vitro. RNA sequencing was performed to explore the effect of metformin on the transcriptome of Huh-7 cells. The results revealed that 4,518 genes (with log2 fold change > 1 or < −1, adjusted p-value < 0.05) were differentially expressed in Huh-7 cells with treatment of 25-mM metformin compared with 0-mM metformin, including 1,812 upregulated and 2,706 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified 54 classical pathways that were significantly enriched, and 16 pathways are closely associated with cancer, such as cell cycle, DNA replication, extracellular matrix–receptor interaction, and so on. We selected 11 differentially expressed genes, which are closely associated with HCC, to validate their differential expressions through a quantitative real-time reverse transcription-polymerase chain reaction. The result exhibited that the genes of fatty acid synthase, mini-chromosome maintenance complex components 6 and 5, myristoylated alanine-rich C-kinase substrate, fatty acid desaturase 2, C-X-C motif chemokine ligand 1, bone morphogenetic protein 4, S-phase kinase-associated protein 2, kininogen 1, and proliferating cell nuclear antigen were downregulated, and Dual-specificity phosphatase-1 is significantly upregulated in Huh-7 cells with treatment of 25-mM metformin. These differentially expressed genes and pathways might play a crucial part in the antitumor effect of metformin and might be potential targets of metformin treating HCC. Further investigations are required to evaluate the metformin mechanisms of anticancer action in vivo.
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spelling pubmed-89854282022-04-07 Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin Li, Chun-Qing Liu, Zhi-Qin Liu, Sha-Sha Zhang, Gao-Tao Jiang, Li Chen, Chuan Luo, Du-Qiang Front Pharmacol Pharmacology Metformin is a kind of widely used antidiabetic drug that regulates glucose homeostasis by inhibiting liver glucose production and increasing muscle glucose uptake. Recently, some studies showed that metformin exhibits anticancer properties in a variety of cancers. Although several antitumor mechanisms have been proposed for metformin action, its mode of action in human liver cancer remains not elucidated. In our study, we investigated the underlying molecular mechanisms of metformin's antitumor effect on Huh-7 cells of hepatocellular carcinoma (HCC) in vitro. RNA sequencing was performed to explore the effect of metformin on the transcriptome of Huh-7 cells. The results revealed that 4,518 genes (with log2 fold change > 1 or < −1, adjusted p-value < 0.05) were differentially expressed in Huh-7 cells with treatment of 25-mM metformin compared with 0-mM metformin, including 1,812 upregulated and 2,706 downregulated genes. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified 54 classical pathways that were significantly enriched, and 16 pathways are closely associated with cancer, such as cell cycle, DNA replication, extracellular matrix–receptor interaction, and so on. We selected 11 differentially expressed genes, which are closely associated with HCC, to validate their differential expressions through a quantitative real-time reverse transcription-polymerase chain reaction. The result exhibited that the genes of fatty acid synthase, mini-chromosome maintenance complex components 6 and 5, myristoylated alanine-rich C-kinase substrate, fatty acid desaturase 2, C-X-C motif chemokine ligand 1, bone morphogenetic protein 4, S-phase kinase-associated protein 2, kininogen 1, and proliferating cell nuclear antigen were downregulated, and Dual-specificity phosphatase-1 is significantly upregulated in Huh-7 cells with treatment of 25-mM metformin. These differentially expressed genes and pathways might play a crucial part in the antitumor effect of metformin and might be potential targets of metformin treating HCC. Further investigations are required to evaluate the metformin mechanisms of anticancer action in vivo. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8985428/ /pubmed/35401213 http://dx.doi.org/10.3389/fphar.2022.822023 Text en Copyright © 2022 Li, Liu, Liu, Zhang, Jiang, Chen and Luo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Chun-Qing
Liu, Zhi-Qin
Liu, Sha-Sha
Zhang, Gao-Tao
Jiang, Li
Chen, Chuan
Luo, Du-Qiang
Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
title Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
title_full Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
title_fullStr Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
title_full_unstemmed Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
title_short Transcriptome Analysis of Liver Cancer Cell Huh-7 Treated With Metformin
title_sort transcriptome analysis of liver cancer cell huh-7 treated with metformin
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985428/
https://www.ncbi.nlm.nih.gov/pubmed/35401213
http://dx.doi.org/10.3389/fphar.2022.822023
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