SERPINA11 Inhibits Metastasis in Hepatocellular Carcinoma by Suppressing MEK/ERK Signaling Pathway.
SERPINA11 Inhibits Metastasis in Hepatocellular Carcinoma by Suppressing MEK/ERK Signaling Pathway.
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SERPINA11 通过抑制 MEK/ERK 信号通路抑制肝细胞癌转移
DOI：
10.2147/jhc.s315634
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发表时间：
2021
影响因子：
4.1
通讯作者：
Zhu YH
中科院分区：
文献类型：
--
作者：
Song Y;Li Z;Li L;Zhou H;Zeng TT;Jin C;Lin JR;Gao S;Li Y;Guan XY;Zhu YH
通过整合RNA测序分析，我们发现了一种新的肿瘤抑制因子，丝氨酸蛋白酶抑制剂家族A成员11（SERPINA 11），这是一种丝氨酸蛋白酶抑制剂，属于丝氨酸蛋白酶抑制剂超家族。然而，SERPINA 11在肝细胞癌（HCC）中的功能仍不清楚。本研究旨在探讨SERPINA 11在肝癌中的作用及其分子机制。通过qRT-PCR分析HCC患者组织样品中SERPINA 11的基因表达模式。通过体内外实验研究SERPINA 11在肿瘤转移中的作用及其分子机制。SERPINA 11在大约50%的HCC中下调，并且与患者的转移和不良预后显著相关。功能研究表明SERPINA 11具有抑制细胞生长、细胞迁移和肿瘤转移的作用。机制研究表明，SERPINA 11加速尿激酶型纤溶酶原激活剂（uPA）降解，抑制细胞外信号调节激酶（ERK 1/2）磷酸化，从而抑制肝癌细胞的转移能力。SERPINA 11在HCC中起着重要的肿瘤抑制作用，可能用作生物标志物和新治疗策略的干预点。
By using integrative RNA sequencing analysis, we identified a novel tumor suppressor, serpin family A member 11 (SERPINA11), which is a serine proteinase inhibitor that belongs to the serpin superfamily. However, the function of SERPINA11 in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the role and molecular mechanism of SERPINA11 in HCC. Gene expression patterns of SERPINA11 were analyzed in tissue samples of HCC patients by qRT-PCR. In vitro and in vivo experiments were performed to characterize the function and molecular mechanism of SERPINA11 in the tumor metastasis capacity. SERPINA11 was downregulated in approximately 50% of HCC and significantly associated with metastasis and poor outcome of patients. Functional study demonstrated that SERPINA11 could inhibit cell growth, cell migration and tumor metastasis. Mechanistic investigations suggested that SERPINA11 accelerated urokinase-type plasminogen activator (uPA) degradation to suppress extracellular signal-regulated kinase (ERK1/2) phosphorylation, and thereby subdued metastatic capabilities of HCC cells. SERPINA11 plays an important tumor suppressive role in HCC, with possible use as a biomarker and an intervention point for new therapeutic strategies.