Elevated expression of eukaryotic translation initiation factor 3H is associated with proliferation, invasion and tumorigenicity in human hepatocellular carcinoma

Oncotarget. 2016 Aug 2;7(31):49888-49901. doi: 10.18632/oncotarget.10222.

Abstract

Aim: We studied the role of eukaryotic translation initiation factor 3 subunit H (EIF3H) in hepatocellular carcinoma (HCC) progression.

Results: High EIF3H expression was observed in 50.23% patients. Upregulation of EIF3H is an independent predictor for greater rates of cancer recurrence and shorter overall survival in HCC patients. Knockdown of EIF3H expression in HCC cells promoted apoptosis, and inhibited cell growth, colony formation, migration, as well as xenograft growth. TGF-βand MAPK pathways are potentially targeted by EIF3H.

Methods: EIF3H mRNA expression was measured in HCC tissue samples and paired non-tumor samples (N=60) and results were validated in another dataset of 215 HCC patients. Then EIF3H expression and clinical outcomes were correlated. Malignant phenotypes were studied after EIF3H expression was knocked down with siRNA in HCC cell lines. EIF3H targeted pathways were identified by microarray analysis.

Conclusion: EIF3H is frequently upregulated and is an independent prognostic marker for HCC patients and EIF3H inhibition mitigates the malignant phenotype. Our data provide novel insight into the function of EIF3H in HCC progression, and suggest that EIF3H may be a potentially valuable biomarker for HCC.

Keywords: hepatocellular carcinoma; initiation factors; microarray; prognosis; tumor progression.

MeSH terms

  • Animals
  • Apoptosis
  • Carcinogenesis
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Eukaryotic Initiation Factor-3 / metabolism*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local
  • Neoplasm Transplantation
  • Prognosis
  • Treatment Outcome

Substances

  • Eukaryotic Initiation Factor-3