Uridine-cytidine kinase 2 upregulation predicts poor prognosis of hepatocellular carcinoma and is associated with cancer aggressiveness

Shanzhou Huang, Jian Li, Nga Lei Tam, Chengjun Sun, Yuchen Hou, Bridget Hughes, Zekang Wang, Qi Zhou, Xiaoshun He, Linwei Wu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Patients with advanced hepatocellular carcinoma (HCC) continue to have a dismal prognosis. Potential biomarkers to determine prognosis and select targeted therapies are urgently needed for patients with HCC. This study aimed to elucidate the role of UCK2 in HCC prognosis and tumor progression. We performed a screen of public databases to identify functional genes associated with HCC tumorigenesis, progression, and outcome. We identified uridine-cytidine kinase 2 (UCK2) as a gene of interest for further study. UCK2 promoting HCC aggressiveness was demonstrated by evaluation of clinical samples, in vitro experiments, in vivo tumorigenicity, and transcript analysis. UCK2 expression was generally elevated in HCC and was significantly correlated with poor survival and inferior clinicopathological characteristics of HCC patients. A multivariate analysis revealed that high UCK2 expression was an independent factor for poor prognosis. In HCC cell lines, UCK2 knockdown suppressed cell migration and invasion and inhibited cell proliferation, while UCK2 overexpression had an opposite effect. Animal model experiments confirmed that knockdown of UCK2 suppressed tumor growth in vivo. The bioinformatics analysis demonstrated that UCK2 might associated with metabolsim, splicesome, and adherens junction. UCK2 is highly associated with HCC malignant behavior and is a potential prognostic predictor for HCC patients in the clinic.

Original languageEnglish (US)
Pages (from-to)603-615
Number of pages13
JournalMolecular Carcinogenesis
Volume58
Issue number4
DOIs
StatePublished - Apr 2019

Keywords

  • UCK2
  • hepatocellular carcinoma
  • prognosis
  • survival analysis
  • tumor progression

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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