Upregulation of Far Upstream Element-Binding Protein 1 (FUBP1) Promotes Tumor Proliferation and Tumorigenesis of Clear Cell Renal Cell Carcinoma

PLoS One. 2017 Jan 11;12(1):e0169852. doi: 10.1371/journal.pone.0169852. eCollection 2017.

Abstract

Objective: The far upstream element (FUSE)-binding protein 1 (FUBP1) is a transactivator of human c-myc proto-oncogene transcription, with important roles in carcinogenesis. However, the expression pattern and potential biological function of FUBP1 in clear cell renal cell carcinoma (ccRCC) is yet to be established.

Methods: FUBP1 expression was detected in ccRCC tissues and cell lines by real-time RT-PCR, Western blot analysis, and immunohistochemistry. The correlations of FUBP1 mRNA expression levels with clinicopathological factors were evaluated. The biological function of FUBP1 during tumor cell proliferation was studied by MTS, colony formation, and soft-agar colony formation. The effects of FUBP1 on cell cycle distribution and apoptosis were analyzed by flow cytometry. Western blot analysis was used to identify the potential mechanism of FUBP1 regulating cell cycle and apoptosis.

Results: The levels of FUBP1 mRNA and protein expression were upregulated in human ccRCC tissues compared with adjacent noncancerous tissues. High levels of FUBP1 mRNA expression were associated with higher tumor stage and tumor size. FUBP1 knockdown inhibited cell proliferation and induced cell cycle arrest and apoptosis. Meanwhile, the expression levels of c-myc and p21 mRNA were correlated with that of FUBP1 mRNA.

Conclusions: FUBP1 acts as a potential oncogene in ccRCC and may be considered as a novel biomarker or an attractive treatment target of ccRCC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cell Transformation, Neoplastic / genetics
  • DNA Helicases / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Proto-Oncogene Mas
  • RNA-Binding Proteins
  • Transcriptional Activation
  • Up-Regulation / genetics

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • FUBP1 protein, human
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • RNA-Binding Proteins
  • DNA Helicases

Grants and funding

This study was supported by the National High Technology Research and Development Program (“863” Program) of China (2014AA020607) and the National Nature and Science Grant of China (81402109).