Purpose: 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.
Methods: 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.
Results: 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.
Conclusion: SERPINA11 plays an important tumor suppressive role in HCC, with possible use as a biomarker and an intervention point for new therapeutic strategies.

Keywords: SERPINA11, HCC, metastasis, uPA, ERK


中文翻译：

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SERPINA11 通过抑制 MEK/ERK 信号通路抑制肝细胞癌的转移

目的：通过整合 RNA 测序分析，我们鉴定了一种新型肿瘤抑制因子，丝氨酸蛋白酶抑制剂家族 A 成员 11 ( SERPINA11 )，它是属于丝氨酸蛋白酶抑制剂超家族的丝氨酸蛋白酶抑制剂。然而，SERPINA11在肝细胞癌 (HCC) 中的功能仍不清楚。本研究旨在探讨SERPINA11在 HCC 中的作用及其分子机制。
方法：通过 qRT-PCR 分析 HCC 患者组织样本中SERPINA11的基因表达模式。进行了体外和体内实验，以表征SERPINA11在肿瘤转移能力中的功能和分子机制。
结果： SERPINA11在大约 50% 的 HCC 中下调，并且与患者的转移和不良预后显着相关。功能研究表明SERPINA11可以抑制细胞生长、细胞迁移和肿瘤转移。机制研究表明，SERPINA11 加速尿激酶型纤溶酶原激活物 (uPA) 降解以抑制细胞外信号调节激酶 (ERK1/2) 磷酸化，从而抑制 HCC 细胞的转移能力。
结论： SERPINA11在HCC中发挥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。

关键词： SERPINA11，HCC，转移，uPA，ERK