GINS1 promotes ZEB1‐mediated epithelial‐mesenchymal transition and tumor metastasis via β‐catenin signaling in hepatocellular carcinoma

Abstract 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.