High expression of FUNDC1 predicts poor prognostic outcomes and is a promising target to improve chemoradiotherapy effects in patients with cervical cancer

Cancer Med. 2017 Aug;6(8):1871-1881. doi: 10.1002/cam4.1112. Epub 2017 Jul 18.

Abstract

FUN14 domain containing 1 (FUNDC1) is an important molecule in receptor-dependent mitophagy. However, the roles of FUNDC1 in human cancer biology remain unknown. The aim of this study was to explore the expression and roles of FUNDC1 in cervical cancer. Immunohistochemistry and Western blotting were applied to detect the expression of FUNDC1, and small-hairpin RNA was applied to inhibit the expression of endogenous FUNDC1 in cervical cancer cells. MTT assays and Flow cytometric analysis were applied to examine cell proliferation and apoptosis. Immunofluorescence was used to detect the formation of γH2AX foci and evaluate the extent of DNA damage. Compared with corresponding adjacent noncancerous cervical tissues, the expression of FUNDC1 in cervical cancer cells was significantly increased. High expression of FUNDC1 and the prognosis of patients with cervical cancer were correlated negatively, which could be used as an independent prognostic factor for overall survival and disease-free survival. Depletion of FUNDC1 significantly inhibited the proliferation of tumor cells, induced apoptosis, and enhanced cell sensitivity to cisplatin and ionizing radiation (IR). Our data suggested that FUNDC1 can be used as a prognostic biomarker in patients with cervical cancer, and may be a new therapeutic target to improve the antitumor effects of chemoradiotherapy.

Keywords: Apoptosis; FUNDC1; cervical cancer; chemoradiotherapy; prognostic biomarker.

MeSH terms

  • Apoptosis / genetics
  • Biomarkers, Tumor*
  • Cell Proliferation
  • Chemoradiotherapy
  • DNA Damage
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • Radiation Tolerance / genetics
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / mortality*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy

Substances

  • Biomarkers, Tumor
  • FUNDC1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins