Background: Targeting protein for Xklp2 (TPX2) is a microtubule-associated protein involved in targeting the motor protein Xklp2 to microtubules. TPX2 overexpression plays a key role in the progression of human cancers. But the underlying mechanism remains unclear.
Aims: This study aimed to investigate the effects and mechanisms of TPX2 on the cell cycle, apoptosis, and epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC).
Methods: The tissue TPX2 mRNA and protein were assessed by quantitative reverse transcriptase PCR and immunoblot. Cell proliferation, cell cycle, apoptosis, and invasion were determined by CCK-8, FACS, TdT-UTP nick end-labeling, and transwell assays. Immunoblotting was performed to detect the expression of target proteins.
Results: TPX2 was highly expressed in tumor tissues compared with non-tumoral tissues, and TPX2 overexpression was positively correlated with poor prognosis. Knockdown TPX2 effectively reduced cell growth, G2/M arrest, induced apoptosis and cell death, and inhibited EMT. Mechanistically, in the TPX2-siRNA-treated groups, cell-cycle-related proteins cyclin A1, cyclin B1, cyclin E1, and cdk4 were up-regulated, while cyclin D1, cdk2, and p21 proteins were down-regulated. Cell-apoptosis-related proteins Bax, p53, caspase-3, and caspase-8 levels were increased. EMT-related proteins E-cadherin was up-regulated, while N-cadherin, β-catenin, MMP-9, MMP-2, and Slug were down-regulated. We also found that knockdown TPX2 in HCC cell lines caused a significant decrease in the level of p-Akt and p-ERK which are important signaling pathways in tumor formation.
Conclusions: TPX2 expression is associated with proliferation, apoptosis, and EMT in hepatocellular carcinoma cell and patients.