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

BMC Cancer

Research Article

Xinhui Zhou¹  Yongxian Hu²  Nong Xu³  Cheng Xiao³  Yulong Zheng³  Lihua Jiang⁴  Jianying Zhou⁵ 

[1] Department of Gynecology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, Zhejiang, China;Department of Hematology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China;Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 310003, Hangzhou, China;Department of Neurology, The Children’s Hospital, School of Medicine, Zhejiang University, 31006, Hangzhou, China;Department of Respiratory Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, 310003, Hangzhou, Zhejiang, China;

关键词: MT1H;    Hepatocellular cancer (HCC);    Proliferation;    Invasion;    Wnt/β-catenin;   

DOI  :  10.1186/s12885-017-3139-2

 received in 2016-07-26, accepted in 2017-02-15,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundMetallothionein 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.MethodsWe 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.ResultsDownregulation 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.ConclusionsThis 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.

【 授权许可】

CC BY   
© The Author(s). 2017