UHRF1 predicts poor prognosis by triggering cell cycle in lung adenocarcinoma

J Cell Mol Med. 2020 Jul;24(14):8069-8077. doi: 10.1111/jcmm.15438. Epub 2020 Jun 3.

Abstract

Accumulating evidence suggests that ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) is overexpressed in non-small cell lung cancer (NSCLC); however, the expression and function of UHRF1 in the subtype of NSCLC are still unclear. Here, we investigate the expression and prognosis traits of UHRF1 in large NSCLC cohorts and explore the molecular characters during UHRF1 up-regulation. We find that UHRF1 is predominantly overexpressed in lung squamous cell carcinoma (SCC). Surprisingly, the up-regulated UHRF1 is only associated with the overall survival of lung adenocarcinoma (ADC) and knockdown of UHRF1 dramatically attenuates ADC tumorigenesis. Mechanically, we identify a hub gene that includes a total of 55 UHRF1-related genes, which are tightly associated with cell cycle pathway and yield to the poor clinical outcome in ADC patients. What's more, we observe knockdown of UHRF1 only affects ADC cells cycle and induces cell apoptosis. These results suggest that up-regulated UHRF1 only contributes to lung ADC survival by triggering cell cycle pathway, and it may be a prognostic biomarker for lung ADC patients.

Keywords: cell cycle; lung adenocarcinoma; non-small cell lung cancer; prognosis; ubiquitin-like with plant homeodomain and ring finger domains 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / mortality*
  • Adenocarcinoma of Lung / pathology
  • Biomarkers, Tumor*
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Cell Cycle / genetics*
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Computational Biology / methods
  • Gene Expression
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Prognosis
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Biomarkers, Tumor
  • CCAAT-Enhancer-Binding Proteins
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases