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ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma

The ATP binding cassette (ABC) transporter family is ubiquitous in eukaryotes, specifically in vertebrates, and plays a crucial role in energy homeostasis, cell signaling, and drug resistance. Accumulating evidence indicates that some ABC transporters contribute to cancer cell proliferation and tumo...

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Autores principales: Zhao, Zhicong, Zhao, Zhenjun, Wang, Jianye, Zhang, He, Xi, Zhifeng, Xia, 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/PMC8907651/
https://www.ncbi.nlm.nih.gov/pubmed/35280774
http://dx.doi.org/10.3389/fonc.2022.840287
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author Zhao, Zhicong
Zhao, Zhenjun
Wang, Jianye
Zhang, He
Xi, Zhifeng
Xia, Qiang
author_facet Zhao, Zhicong
Zhao, Zhenjun
Wang, Jianye
Zhang, He
Xi, Zhifeng
Xia, Qiang
author_sort Zhao, Zhicong
collection PubMed
description The ATP binding cassette (ABC) transporter family is ubiquitous in eukaryotes, specifically in vertebrates, and plays a crucial role in energy homeostasis, cell signaling, and drug resistance. Accumulating evidence indicates that some ABC transporters contribute to cancer cell proliferation and tumor progression; however, relatively little is known about the behavior of the ABC transporter family in hepatocellular carcinoma (HCC). By analyzing two public transcriptomic databases, we evaluated the effect of genes in the ABC transporter family on HCC prognostic prediction; ABCC6 was selected for further study. Notably, ABCC6 was found to be downregulated in HCC tissues and correlated with favorable outcomes in patients with HCC. Moreover, ABCC6 knockdown not only significantly promoted cell proliferation in vitro and in vivo, but also inhibited cell cycle arrest and cell apoptosis. Transcriptome analysis revealed that ABCC6 depletion enhanced the “mitotic cell cycle” and “DNA replication” pathways, and suppressed the “PPAR signaling pathway”. Further investigation demonstrated that PPARα, one of the key regulators in peroxisome metabolism, is located downstream of ABCC6. In summary, our study provides profound insights into the behavior of ABC transporter family genes in various HCC cohorts, identifies ABCC6 as a biomarker for early-stage HCC diagnosis, and offers experimental basis for further investigations of targeting ABCC6 in the treatment of patients with HCC.
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spelling pubmed-89076512022-03-11 ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma Zhao, Zhicong Zhao, Zhenjun Wang, Jianye Zhang, He Xi, Zhifeng Xia, Qiang Front Oncol Oncology The ATP binding cassette (ABC) transporter family is ubiquitous in eukaryotes, specifically in vertebrates, and plays a crucial role in energy homeostasis, cell signaling, and drug resistance. Accumulating evidence indicates that some ABC transporters contribute to cancer cell proliferation and tumor progression; however, relatively little is known about the behavior of the ABC transporter family in hepatocellular carcinoma (HCC). By analyzing two public transcriptomic databases, we evaluated the effect of genes in the ABC transporter family on HCC prognostic prediction; ABCC6 was selected for further study. Notably, ABCC6 was found to be downregulated in HCC tissues and correlated with favorable outcomes in patients with HCC. Moreover, ABCC6 knockdown not only significantly promoted cell proliferation in vitro and in vivo, but also inhibited cell cycle arrest and cell apoptosis. Transcriptome analysis revealed that ABCC6 depletion enhanced the “mitotic cell cycle” and “DNA replication” pathways, and suppressed the “PPAR signaling pathway”. Further investigation demonstrated that PPARα, one of the key regulators in peroxisome metabolism, is located downstream of ABCC6. In summary, our study provides profound insights into the behavior of ABC transporter family genes in various HCC cohorts, identifies ABCC6 as a biomarker for early-stage HCC diagnosis, and offers experimental basis for further investigations of targeting ABCC6 in the treatment of patients with HCC. Frontiers Media S.A. 2022-02-24 /pmc/articles/PMC8907651/ /pubmed/35280774 http://dx.doi.org/10.3389/fonc.2022.840287 Text en Copyright © 2022 Zhao, Zhao, Wang, Zhang, Xi and Xia 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 Oncology
Zhao, Zhicong
Zhao, Zhenjun
Wang, Jianye
Zhang, He
Xi, Zhifeng
Xia, Qiang
ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
title ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
title_full ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
title_fullStr ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
title_full_unstemmed ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
title_short ABCC6 Knockdown Fuels Cell Proliferation by Regulating PPARα in Hepatocellular Carcinoma
title_sort abcc6 knockdown fuels cell proliferation by regulating pparα in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907651/
https://www.ncbi.nlm.nih.gov/pubmed/35280774
http://dx.doi.org/10.3389/fonc.2022.840287
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