Methionine Sulfoxide Reductase B1 Regulates Hepatocellular Carcinoma Cell Proliferation and Invasion via the Mitogen-Activated Protein Kinase Pathway and Epithelial-Mesenchymal Transition.

Qiang He,Jiang Chen,Libo Li,Xu Feng,Hui Li,Jinghua Liu,Fanzhi Meng,Xiangjun Sun

doi:10.1155/2018/5287971

Abstract

Methionine sulfoxide reductase B1 (MsrB1) is a member of the selenoprotein family, which contributes to the reduction of methionine sulfoxides produced from reactive oxygen species (ROS) by redox processes in energy pathways. However, few studies have examined the role of MsrB1 in human hepatocellular carcinoma (HCC). We observed that MsrB1 is highly expressed in HCC tissues and that its expression correlated with the prognoses of patients with HCC after hepatectomy. In vitro, knockdown of MsrB1 inhibits HCC cell growth by MTT and EdU proliferation assay, and MsrB1 interference enhances H2O2/trx-induced apoptosis. We observed that phosphorylation of the key proteins of the MAPK pathway, namely, ERK, MEK, and p53, was inhibited, but PARP and caspase 3 were increased, thus infecting mitochondrial integrity. In vivo, MsrB1 knockdown effectively inhibited tumor growth. Furthermore, MsrB1 knockdown reduced HCC cell migration and invasion in a transwell assay through inhibition of cytoskeletal rearrangement and spread. This change was linked to epithelial-mesenchymal transition (EMT) inhibition resulting from increases in E-cadherin expression and decreases in expression in TGF-β1, Slug, MMP-2/9, and so on. MsrB1 regulates HCC cell proliferation and migration by modulating the MAPK pathway and EMT. Thus, MsrB1 may be a novel therapeutic target with respect to the treatment of HCC.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and causes half a million deaths each year
Upregulation of Methionine sulfoxide reductase B1 (MsrB1) in HCC Is Correlated with Poor Prognosis
We found that MsrB1 mRNA expression was upregulated in 5 of the 6 HCC tissue samples compared with 8 of the 9 tumor-free liver disease tissue samples (Figure 1(a))

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and causes half a million deaths each year. Among the antioxidant enzymes induced by reactive oxygen species (ROS), methionine sulfoxide reductases (MSRs) are unique in their ability to direct protein repair and indirectly scavenge ROS. Within this subfamily, MsrB1, a selenoprotein that contains a selenocysteine residue in place of the catalytic cysteine residue normally present in other MsrBs [1, 2], displays high catalytic activity toward protein-based R-Met(O) and low efficient activity toward free Met(O) [2]. MsrB1 interfered with HCC cell proliferation and invasion in vitro/ in vivo This change was linked to related processes of the mitogen-activated protein kinase (MAPK) pathway and epithelial-mesenchymal transition (EMT).

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Results

Conclusion