FBXW7γ is a tumor-suppressive and prognosis-related FBXW7 transcript isoform in ovarian serous cystadenocarcinoma

Future Oncol. 2020 Sep;16(25):1921-1930. doi: 10.2217/fon-2020-0371. Epub 2020 Jun 17.

Abstract

Aim: To explore FBXW7 protein-coding transcript isoform (α, β and γ) expression, their functions and prognostic value in ovarian serous cystadenocarcinoma (OSC). Materials & methods: FBXW7 transcript data were collected from The Cancer Genome Atlas and the Genotype-Tissue Expression project. IOSE, A2780 and SKOV3 cells were used for in vitro and in vivo studies. Results: FBXW7α and FBXW7γ are dominant protein-coding transcripts that were downregulated in OSC. FBXW7γ overexpression reduced the protein expression of c-Myc, Notch1 and Yap1 and suppressed OSC cell growth in vitro and in vivo. FBXW7γ expression was an independent indicator of longer disease-specific survival (HR: 0.588; 95% CI: 0.449-0.770) and progression-free survival (HR: 0.708; 95% CI: 0.562-0.892). Conclusion: FBXW7γ is a tumor-suppressive and might be the only prognosis-related FBXW7 transcript in OSC.

Keywords: ENST00000296555; FBXW7; ovarian serous cystadenocarcinoma; prognosis.

MeSH terms

  • Alternative Splicing*
  • Animals
  • Biomarkers, Tumor*
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous / etiology*
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / mortality*
  • Cystadenocarcinoma, Serous / pathology
  • Disease Models, Animal
  • F-Box-WD Repeat-Containing Protein 7 / genetics*
  • Fallopian Tubes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Ovarian Neoplasms / etiology*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Prognosis
  • RNA Isoforms
  • RNA, Messenger / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • RNA Isoforms
  • RNA, Messenger