Department of Hepatobiliary Surgery, Linyi People's Hospital, 27th of East Jiefang Road, Linyi, Shandong 276000, China.
Human Resource Department, Linyi People's Hospital, 27th of East Jiefang Road, Linyi, Shandong 276000, China.
Oxid Med Cell Longev. 2018 May 10;2018:5287971. doi: 10.1155/2018/5287971. eCollection 2018.
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. , knockdown of MsrB1 inhibits HCC cell growth by MTT and EdU proliferation assay, and MsrB1 interference enhances HO/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. , 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-1, 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.
甲硫氨酸亚砜还原酶 B1（MsrB1）是硒蛋白家族的成员，通过能量途径中的氧化还原过程，有助于还原活性氧（ROS）产生的蛋氨酸亚砜。然而，很少有研究探讨 MsrB1 在人肝细胞癌（HCC）中的作用。我们观察到 MsrB1 在 HCC 组织中高表达，其表达与 HCC 患者肝切除术后的预后相关。此外，通过 MTT 和 EdU 增殖试验，敲低 MsrB1 抑制 HCC 细胞生长，MsrB1 干扰增强 HO/trx 诱导的细胞凋亡。我们观察到 MAPK 通路的关键蛋白 ERK、MEK 和 p53 的磷酸化受到抑制，但 PARP 和 caspase 3 增加，从而影响线粒体完整性。体内研究表明，MsrB1 敲低有效地抑制了肿瘤生长。此外，通过抑制细胞骨架重排和扩展，MsrB1 敲低在 Transwell 测定中有效抑制了 HCC 细胞的迁移和侵袭。这种变化与上皮-间充质转化（EMT）的抑制有关，这是由于 E-钙黏蛋白表达增加和 TGF-β1、Slug、MMP-2/9 等表达减少所致。MsrB1 通过调节 MAPK 通路和 EMT 调节 HCC 细胞的增殖和迁移。因此，MsrB1 可能是治疗 HCC 的一个新的治疗靶点。
