Preliminary Study of the Role F-Box Protein 32 (FBXO32) in Colorectal Neoplasms Through the Transforming Growth Factor beta (TGF-β)/Smad4 Signalling Pathway

Med Sci Monit. 2018 Feb 21;24:1080-1088. doi: 10.12659/msm.908030.

Abstract

BACKGROUND F-box protein 32 (FBXO32) (also known as atrogin-1), a member of the F-box protein family, was recently shown to be a transforming growth factor beta (TGF-β)/Smad4 target gene involved in regulating cell survival. It can be transcriptionally silenced by epigenetic mechanisms in some cancers, but its role in colorectal carcinoma (CRC) is unclear. We investigated the role of FBXO32 in CRC and determined its prognostic significance. MATERIAL AND METHODS We used real-time quantitative PCR, Western blot, and immunohistochemistry to elucidate the role of FBXO32 in clinical specimens and primary CRC cell lines. Differences in patient survival were determined by the Kaplan-Meier method and log-rank test. RESULTS We found that the FBXO32 and SMAD4 levels were higher in normal tissues than in CRC tissues, but PAI-1 and VEGF levels showed the opposite pattern. The expressions of FBXO32 and SMAD4 were related to clinicopathological parameters in CRC. Kaplan-Meier analyses showed that the 5-year overall survival of the low-FBXO32 expression group was significantly shorter than that of the high-FBXO32 expression group (p=0.010). CONCLUSIONS The fbxo32 gene is a novel tumor suppressor that inhibits CRC progression by inducing differentiation. Elevated expression of FBXO32 predicts longer survival in CRC patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Epigenesis, Genetic
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Muscle Proteins / metabolism*
  • Prognosis
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Signal Transduction
  • Smad4 Protein / metabolism*
  • Transforming Growth Factor beta / metabolism

Substances

  • Biomarkers, Tumor
  • Muscle Proteins
  • SMAD4 protein, human
  • Smad4 Protein
  • Transforming Growth Factor beta
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases