MYC associated zinc finger protein promotes the invasion and metastasis of hepatocellular carcinoma by inducing epithelial mesenchymal transition

Wei Luo,Xueyan Miao,Xiaonian Zhu,Chunhua Bei,Shengkui Tan,Yuan Ren,Guifang Tang,Fen Tang,Wei Liu,Linyuan Qin

doi:10.18632/oncotarget.13416

Wei Luo, Xueyan Miao + Show 8 more

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https://doi.org/10.18632/oncotarget.13416

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Journal: Oncotarget	Publication Date: Nov 16, 2016
Citations: 38	License type: cc-by

Affiliation: Guilin Medical University

Abstract

MYC associated zinc finger protein (MAZ) plays a key role in regulation of gene expression and tumor development. Studies have shown that deregulated expression of MAZ is closely related to the progression of tumors such as glioblastoma, breast cancer, prostate cancer and liposarcoma. However, the role of MAZ in hepatocellular carcinoma (HCC) has not been fully elucidated. Here, we found that expression of MAZ was increased in HCC and correlated to the distant metastasis of HCC. Moreover, we found that MAZ had a relationship with zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), two important mesenchymal markers in epithelial-mesenchymal transition (EMT) that were over-expressed in HCC. After knocking-down MAZ expression in HCC cell lines using RNA interruption, HCC cell proliferation, tumorigenesis, invasion and migration were significantly inhibited. In addition, we found that expression of other EMT markers was also changed besides ZEB1 and ZEB2 by decreasing MAZ expression, both detected in vivo and in vitro assays. Therefore, we conclude that MAZ can promote the invasion and metastasis of HCC by inducing EMT.

Highlights

Hepatocellular carcinoma (HCC) is a common malignant tumor of digestive system, a consequence from the interaction between environmental and genetic factors, and its incidence has close relationship with gender, geographic location and family history of patients [1]
We found that MYC associated zinc finger protein (MAZ) had a relationship with zinc finger E-box binding homeobox 1 and 2 (ZEB1 and ZEB2), two important mesenchymal markers in epithelialmesenchymal transition (EMT) that were over-expressed in hepatocellular carcinoma (HCC)
In order to investigate the relationship between MAZ and HCC, we firstly examined protein expression of MAZ in 23 pairs of HCC and adjacent non-tumor tissues by Western blot

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common malignant tumor of digestive system, a consequence from the interaction between environmental and genetic factors, and its incidence has close relationship with gender, geographic location and family history of patients [1]. Recent reports show there are about 800,000 new cases of HCC around the world each year, of which more than 50% occurred in China [2, 3]. There are 60%–70% or more of HCC patients have recurrence during 5 years after surgery in China. Extensive research has been attracted to identify the mechanism of pathogenesis and carcinogenesis, markers or targets of diagnosis, treatment and prognosis on HCC [6,7,8]. The exact molecular pathogenesis of HCC is still not fully understood and the current prognostic markers are still not satisfactory either in terms of accuracy or repeatability.

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