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

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.

Liang J ，Yao N ，Deng B ，Li J ，Jiang Y ，Liu T ，Hu Y ，Cao M ，Hong J ... -  《-》

LncRNA HULC enhances epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma via the miR-200a-3p/ZEB1 signaling pathway.

Li SP ，Xu HX ，Yu Y ，He JD ，Wang Z ，Xu YJ ，Wang CY ，Zhang HM ，Zhang RX ，Zhang JJ ，Yao Z ，Shen ZY ... -  《Oncotarget》

ARHGEF11 promotes proliferation and epithelial-mesenchymal transition of hepatocellular carcinoma through activation of β-catenin pathway.

Du J ，Zhu Z ，Xu L ，Chen X ，Li X ，Lan T ，Li W ，Yuan K ，Zeng Y ... -  《Aging-US》

HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling.

Heart development protein with EGF-like domains 1 (HEG1) plays critical roles in embryo development and angiogenesis, which are closely related to tumor progression. However, the role of HEG1 in hepatocellular carcinoma (HCC) remains unknown. In the present study, we explored the clinical significance, biological function and regulatory mechanisms of HEG1 in HCC and found that HEG1 is significantly up-regulated in HCC cell lines and primary tumor samples. Additionally, high HEG1 expression is correlated with aggressive clinicopathological features. Patients with high HEG1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with low HEG1 expression, which indicated that HEG1 is an independent factor for poor prognosis. Lentivirus-mediated HEG1 overexpression significantly promotes HCC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro and promotes intrahepatic metastasis, lung metastasis and EMT in vivo Opposing results are observed when HEG1 is silenced. Mechanistically, HEG1 promotes β-catenin expression and maintains its stability, leading to intracellular β-catenin accumulation, β-catenin nuclear translocation and Wnt signaling activation. Loss- and gain-of-function assays further confirmed that β-catenin is essential for HEG1-mediated promotion of HCC invasion, metastasis and EMT. In conclusion, HEG1 indicates poor prognosis; plays important roles in HCC invasion, metastasis and EMT by activating Wnt/β-catenin signaling; and can serve as a potentially valuable prognostic biomarker and therapeutic target for HCC.

Zhao YR ，Wang JL ，Xu C ，Li YM ，Sun B ，Yang LY ... -  《-》

TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin.

Yuan K ，Xie K ，Lan T ，Xu L ，Chen X ，Li X ，Liao M ，Li J ，Huang J ，Zeng Y ，Wu H ... -  《-》