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Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway

BACKGROUND: Metallothionein 1H (MT1H) expression level is downregulated in several kinds of tumors, including hepatocellular cancer (HCC). However, its biological functions and underlying mechanisms in HCC is largely unknown. The current study aimed to demonstrate the expression status, biological r...

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Autores principales: Zheng, Yulong, Jiang, Lihua, Hu, Yongxian, Xiao, Cheng, Xu, Nong, Zhou, Jianying, Zhou, Xinhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330125/
https://www.ncbi.nlm.nih.gov/pubmed/28241806
http://dx.doi.org/10.1186/s12885-017-3139-2
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author Zheng, Yulong
Jiang, Lihua
Hu, Yongxian
Xiao, Cheng
Xu, Nong
Zhou, Jianying
Zhou, Xinhui
author_facet Zheng, Yulong
Jiang, Lihua
Hu, Yongxian
Xiao, Cheng
Xu, Nong
Zhou, Jianying
Zhou, Xinhui
author_sort Zheng, Yulong
collection PubMed
description BACKGROUND: Metallothionein 1H (MT1H) expression level is downregulated in several kinds of tumors, including hepatocellular cancer (HCC). However, its biological functions and underlying mechanisms in HCC is largely unknown. The current study aimed to demonstrate the expression status, biological roles and potential mechanisms of MT1H in HCC. METHODS: We investigated the expression level of MT1H in the Cancer Genome Atlas (TCGA) dataset and a panel of 12 paired tumor/non-tumor tissues. In vitro, gain-of-function experiments were performed to examine the role of MT1H on HCC cell proliferation, invasion, and migration. Using bioinformatics assay, reporter assays, quantitative real-time PCR, and western blotting, we explored the possible mechanisms underlying the role of MT1H in HCC cells. In vivo nude mice experiments were performed to assess the anti-proliferative role of MT1H in HCC. RESULTS: Downregulation of MT1H was observed in TCGA dataset and a panel of 12 paired tumor/non-tumor tissues. Ectopic overexpression of MT1H in HepG2 and Hep3B cells inhibited cell proliferation, invasion, and migration. Gene Set Enrichment Analysis (GSEA) showed that MT1H might involve in regulation of Wnt/β-catenin pathway. Top/Fop reporter assay confirmed that MT1H had an effect on Wnt/β-catenin signaling. Real-time PCR showed MT1H expression decreased the expression of Wnt/β-catenin target genes. Western blotting assay showed that overexpression of MT1H inhibited the nuclear translocation of β-catenin and that the Akt/GSK-3β axis mediated the modulatory role of MT1H on Wnt/β-catenin signaling in HCC. In vivo nude mice experiments demonstrated that MT1H suppressed the proliferation of HCC cells. Taken together, MT1H suppressed the proliferation, invasion and migration of HCC cells via regulating Wnt/β-catenin signaling pathway. CONCLUSIONS: This study demonstrated that through inhibiting Wnt/β-catenin pathway, MT1H suppresses the proliferation and invasion of HCC cells. MT1H may be a potential target for HCC therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3139-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-53301252017-03-03 Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway Zheng, Yulong Jiang, Lihua Hu, Yongxian Xiao, Cheng Xu, Nong Zhou, Jianying Zhou, Xinhui BMC Cancer Research Article BACKGROUND: Metallothionein 1H (MT1H) expression level is downregulated in several kinds of tumors, including hepatocellular cancer (HCC). However, its biological functions and underlying mechanisms in HCC is largely unknown. The current study aimed to demonstrate the expression status, biological roles and potential mechanisms of MT1H in HCC. METHODS: We investigated the expression level of MT1H in the Cancer Genome Atlas (TCGA) dataset and a panel of 12 paired tumor/non-tumor tissues. In vitro, gain-of-function experiments were performed to examine the role of MT1H on HCC cell proliferation, invasion, and migration. Using bioinformatics assay, reporter assays, quantitative real-time PCR, and western blotting, we explored the possible mechanisms underlying the role of MT1H in HCC cells. In vivo nude mice experiments were performed to assess the anti-proliferative role of MT1H in HCC. RESULTS: Downregulation of MT1H was observed in TCGA dataset and a panel of 12 paired tumor/non-tumor tissues. Ectopic overexpression of MT1H in HepG2 and Hep3B cells inhibited cell proliferation, invasion, and migration. Gene Set Enrichment Analysis (GSEA) showed that MT1H might involve in regulation of Wnt/β-catenin pathway. Top/Fop reporter assay confirmed that MT1H had an effect on Wnt/β-catenin signaling. Real-time PCR showed MT1H expression decreased the expression of Wnt/β-catenin target genes. Western blotting assay showed that overexpression of MT1H inhibited the nuclear translocation of β-catenin and that the Akt/GSK-3β axis mediated the modulatory role of MT1H on Wnt/β-catenin signaling in HCC. In vivo nude mice experiments demonstrated that MT1H suppressed the proliferation of HCC cells. Taken together, MT1H suppressed the proliferation, invasion and migration of HCC cells via regulating Wnt/β-catenin signaling pathway. CONCLUSIONS: This study demonstrated that through inhibiting Wnt/β-catenin pathway, MT1H suppresses the proliferation and invasion of HCC cells. MT1H may be a potential target for HCC therapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-017-3139-2) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-28 /pmc/articles/PMC5330125/ /pubmed/28241806 http://dx.doi.org/10.1186/s12885-017-3139-2 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zheng, Yulong
Jiang, Lihua
Hu, Yongxian
Xiao, Cheng
Xu, Nong
Zhou, Jianying
Zhou, Xinhui
Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway
title Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway
title_full Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway
title_fullStr Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway
title_full_unstemmed Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway
title_short Metallothionein 1H (MT1H) functions as a tumor suppressor in hepatocellular carcinoma through regulating Wnt/β-catenin signaling pathway
title_sort metallothionein 1h (mt1h) functions as a tumor suppressor in hepatocellular carcinoma through regulating wnt/β-catenin signaling pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330125/
https://www.ncbi.nlm.nih.gov/pubmed/28241806
http://dx.doi.org/10.1186/s12885-017-3139-2
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