title: TPX2 Level Correlates with Hepatocellular Carcinoma Cell Proliferation, Apoptosis, and EMT.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China, lb2087@163.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.forename: Chunhong
authors.initials: C
authors.lastname: Jia
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.forename: Jialu
authors.initials: J
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Liao
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Xincheng
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
authors.forename: Dinghua
authors.initials: D
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000503:physiopathology*; D018797:Cell Cycle Proteins / Q000097:blood*; D049109:Cell Proliferation / Q000502:physiology*; D016213:Cyclins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000097:blood*; D008875:Middle Aged; D009687:Nuclear Proteins / Q000097:blood*; D011379:Prognosis; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018797:Cell Cycle Proteins; D016213:Cyclins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; C122167:TPX2 protein, human