MCM7 promotes cancer progression through cyclin D1-dependent signaling and serves as a prognostic marker for patients with hepatocellular carcinoma

Cell Death Dis. 2017 Feb 9;8(2):e2603. doi: 10.1038/cddis.2016.352.

Abstract

DNA replication is a central procedure of cell proliferation, whereas aberrant DNA replication is indicated to be a driving force of oncogenesis. Minichromosome maintenance complex component 7 (MCM7) plays an essential role in initiating DNA replication. To investigate the potential oncogenic properties and prognostic value of MCM7 in hepatocellular carcinoma (HCC), we conducted immunohistochemistry staining of MCM7 in 153 HCC samples and found that MCM7 high expression level was associated with worse overall survival (OS) of HCC patients. Mechanistically, knockdown of MCM7 significantly inhibited cellular proliferation in vitro and HCC tumorigenicity in vivo. Cyclin D1 was proved to be regulated by MCM7-MAPK signaling pathway. Clinically, high expression of both MCM7 and cyclin D1 exhibited a relatively high sensitivity and specificity to predict worse outcome of HCC patients. Taken together, our results suggest that MCM7-cyclin D1 pathway may participate in cancer progression and serve as a biomarker for prognosis in HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / physiology
  • Cyclin D1 / metabolism*
  • DNA Replication / physiology
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Minichromosome Maintenance Complex Component 7 / metabolism*
  • Nuclear Proteins / metabolism
  • Prognosis
  • Signal Transduction / physiology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Cyclin D1
  • MCM7 protein, human
  • Minichromosome Maintenance Complex Component 7