Far upstream element-binding protein 1 (FUBP1) is a potential c-Myc regulator in esophageal squamous cell carcinoma (ESCC) and its expression promotes ESCC progression

Tumour Biol. 2016 Mar;37(3):4115-26. doi: 10.1007/s13277-015-4263-8. Epub 2015 Oct 21.

Abstract

The human far upstream element (FUSE) binding protein 1 (FUBP1) belongs to an ancient family which is required for proper regulation of the c-Myc proto-oncogene. Although c-Myc plays an important role in development of various carcinomas, the relevance of FUBP1 and their contribution to esophageal squamous cell carcinoma (ESCC) development remain unclear. In this study, we aimed to investigate the relationship between FUBP1 and c-Myc as well as their contribution to ESCC development. Western blot and immunohistochemical analyses were performed to evaluate FUBP1 expression. Coimmunoprecipitation analysis was performed to explore the correlation between FUBP1 and c-Myc in ESCC. In addition, the role of FUBP1 in ESCC proliferation was studied in ESCC cells through knocking FUBP1 down. The regulation of FUBP1 on proliferation was confirmed by Cell Counting Kit-8 (CCK-8) assay, flow cytometric assays, and clone formation assays. The expressions of FUBP1 and c-Myc were both upregulated in ESCC tissues. In addition to correlation between expression of FUBP1 and tumor grade, we also confirmed the correlation of FUBP1, c-Myc, and Ki-67 expression by twos. Moreover, upregulation of FUBP1 and c-Myc in ESCC was associated with poor survival. FUBP1 was confirmed to activate c-Myc in ESCC tissues and cells. FUBP1 was demonstrated to promote proliferation of ESCC cells. Moreover, downregulation of both FUBP1 and c-Myc was confirmed to inhibit proliferation of ESCC cells. Our results indicated that FUBP1 may potentially stimulate c-Myc expression in ESCC and its expression may promote ESCC progression.

Keywords: Esophageal squamous cell carcinoma (ESCC); FUBP1; Proliferation; c-Myc.

MeSH terms

  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA Helicases / physiology*
  • DNA-Binding Proteins / physiology*
  • Disease Progression
  • Down-Regulation
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagus / metabolism
  • Esophagus / pathology
  • Female
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA-Binding Proteins

Substances

  • DNA-Binding Proteins
  • FUBP1 protein, human
  • MAS1 protein, human
  • MYC protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-myc
  • RNA-Binding Proteins
  • DNA Helicases