Peroxiredoxin 4 promotes embryonal hepatoblastoma cell migration but induces fetal cell differentiation.
Peroxiredoxin 4 promotes embryonal hepatoblastoma cell migration but induces fetal cell differentiation.
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发表时间：
2020-06
影响因子：
2.2
通讯作者：
Jianbo Zheng;Xin Guo;A. Shioya;T. Yoshioka;Kimikazu Matsumoto;T. Hiraki;Hironori Kusano;T. Oyama;N. Kurose;R. Yamaguchi;H. Uramoto;S. Ieiri;H. Okajima;M. Kohno;S. Yamada
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作者：
Jianbo Zheng;Xin Guo;A. Shioya;T. Yoshioka;Kimikazu Matsumoto;T. Hiraki;Hironori Kusano;T. Oyama;N. Kurose;R. Yamaguchi;H. Uramoto;S. Ieiri;H. Okajima;M. Kohno;S. Yamada
肝母细胞瘤（HB）是儿童中主要的原发性肝脏恶性肿瘤，可能是由于肝祖细胞无法正确分化而出现的。Peroxiredoxin（PRDX）家族通常与癌症有关。在我们以前的研究中，我们证明了唯一的分泌型家族成员PRDX 4的表达与肝细胞癌相关。这项新研究的目的是研究PRDX 4在HB中的作用。我们收集了87例HB标本，并进行PRDX 4免疫组化染色。进行了临床分析，并检查了PRDX 4过表达对两种HB细胞系（Huh 6和HepG 2）的影响。临床数据显示，胚胎成分中PRDX 4表达升高与晚期（IV）和转移相关。相比之下，胎儿成分中PRDX 4表达增加与分化良好相关。体外实验表明，PRDX 4过表达增强了胚胎样HB细胞（Huh 6）的迁移，并伴有上皮-间质转化（EMT）。相比之下，PRDX 4过表达抑制增殖，减少干细胞标志物，并增加胎儿样HB细胞（HepG 2）中的肝标志物，这表明诱导肿瘤细胞分化。总之，PRDX 4促进胚胎肝母细胞瘤细胞迁移，但诱导胎儿细胞分化。它可作为乙肝预后的重要指标和潜在的治疗靶点。
Hepatoblastoma (HB) is the leading primary hepatic malignancy in children and likely emerges due to failure of hepatic progenitor cells to properly differentiate. The peroxiredoxin (PRDX) family is frequently linked to cancer. In our previous study, we demonstrated that expression of the only secreted family member, PRDX4, was correlated with hepatocellular carcinoma. The aim of this new study was to investigate PRDX4's role in HB. We collected 87 HB specimens and performed PRDX4 immunohistochemistry staining. Clinical analysis was conducted and the effect of PRDX4 overexpression on two HB cell lines (Huh6 and HepG2) was also examined. Clinical data revealed elevated PRDX4 expression in embryonal component was correlated with advanced stage (IV) and metastasis. In comparison, increased PRDX4 expression in fetal component was associated with well differentiation. In vitro experiments showed PRDX4 overexpression enhanced migration in embryonal-like HB cells (Huh6), which was accompanied by epithelial-mesenchymal transition (EMT). By contrast, PRDX4 overexpression inhibited proliferation, decreased stemness markers, and increased hepatic markers in fetal-like HB cells (HepG2), which indicated induction of tumor cell differentiation. In conclusion, PRDX4 promotes embryonal hepatoblastoma cell migration but induces fetal cell differentiation. It can be adopted as an important marker for HB prognosis and a potential treatment target.