Department of Hepatobiliary Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, China.
Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, China.
J Cell Physiol. 2024 May;239(5):e31237. doi: 10.1002/jcp.31237. Epub 2024 Mar 11.
GINS1 regulates DNA replication in the initiation and elongation phases and plays an important role in the progression of various malignant tumors. However, the role of GINS1 in hepatocellular carcinoma (HCC) remains largely unclear. In this study, we investigated the role and underlying mechanisms of GINS1 in contributing to HCC metastasis. We found that GINS1 was significantly upregulated in HCC tissues and cell lines, especially in HCC tissues with vascular invasion and HCC cell lines with highly metastatic properties. Additionally, high expression of GINS1 was positively correlated with the progressive clinical features of HCC patients, including tumor number (multiple), tumor size (>5 cm), advanced tumor stage, vascular invasion and early recurrence, suggesting that GINS1 upregulation was greatly involved in HCC metastasis. Moreover, Kaplan-Meier survival analysis revealed that high GINS1 expression predicted a poor prognosis. Both in vitro and in vivo, silencing of GINS1 inhibited proliferation, migration, invasion and metastasis, while overexpression of GINS1 induced opposite effects. Mechanistically, we found that ZEB1 was a crucial regulator of GINS1-induced epithelial-mesenchymal transition (EMT), and GINS1 promoted EMT and tumor metastasis through β-catenin signaling. Overall, the present study demonstrated that GINS1 promoted ZEB1-mediated EMT and tumor metastasis via β-catenin signaling in HCC.
GINS1 调节 DNA 复制的起始和延伸阶段，在各种恶性肿瘤的进展中发挥重要作用。然而，GINS1 在肝细胞癌（HCC）中的作用在很大程度上仍不清楚。在这项研究中，我们研究了 GINS1 在促进 HCC 转移中的作用和潜在机制。我们发现 GINS1 在 HCC 组织和细胞系中显著上调，尤其是在具有血管侵犯的 HCC 组织和具有高转移性特性的 HCC 细胞系中。此外，GINS1 的高表达与 HCC 患者进行性临床特征呈正相关，包括肿瘤数量（多个）、肿瘤大小（>5cm）、肿瘤分期较晚、血管侵犯和早期复发，表明 GINS1 上调与 HCC 转移密切相关。此外，Kaplan-Meier 生存分析显示，GINS1 高表达预示着预后不良。在体外和体内，沉默 GINS1 均抑制增殖、迁移、侵袭和转移，而过表达 GINS1 则诱导相反的效果。在机制上，我们发现 ZEB1 是 GINS1 诱导的上皮-间充质转化（EMT）的关键调节因子，GINS1 通过 β-catenin 信号通路促进 EMT 和肿瘤转移。总体而言，本研究表明 GINS1 通过 β-catenin 信号通路促进 ZEB1 介导的 EMT 和 HCC 中的肿瘤转移。
