Silencing of FANCI Promotes DNA Damage and Sensitizes Ovarian Cancer Cells to Carboplatin

Curr Cancer Drug Targets. 2022;22(7):591-602. doi: 10.2174/1568009622666220331091709.


Background: Ovarian cancer (OVCA) has unique epigenetic alterations and defects in homologous recombination (HR). Despite initial sensitivity to platinum-based chemotherapy, HR dysfunctional tumors eventually acquire drug resistance. Fanconi anemia (FA) is characterized by bone marrow failure (BMF) and a reduced ability to eradicate DNA interstrand cross-links (ICL). However, the mechanism of chemoresistance mediated by FANCI was unclear in OVCA.

Objective: We explore to identify whether FANCI was involved in chemoresistance in OVCA.

Methods: FANCI expression and epigenetic alterations were analyzed, respectively, using TIMER and cBioPortal. The correlation between FANCI expression and the survival of OVCA patients was analyzed using Kaplan-Meier Plotter, GSE63885, and TCGA-OVCA dataset. FANCI expression in OVCA was detected by immunohistochemistry. Cell proliferation, migration, and invasion in FANCI inhibiting cells were assessed by CCK-8 and Transwell. Apoptosis and DNA damage were examined by flow cytometry and immunofluorescence. Meanwhile, the activity of caspase 3/7 was detected by Caspase-Glo® 3/7 kit. In addition, the expression of FANCI, γH2AX, and apoptosis effectors was examined by Western blot.

Results: FANCI has copy number variations (CNVs) in OVCA. The high expression of FANCI in OVCA patients was associated with poor survival. Moreover, FANCI expression was correlated with the response to chemotherapy in OVCA. FANCI expression in OVCA cells was induced by carboplatin in a time-dependent manner. Silencing of FANCI had no effect on cell proliferation, but hindered OVCA cell migration and invasion. Mechanically, knockdown of FANCI enhanced DNA damage-induced apoptosis through the CHK1/2-P53-P21 pathway.

Conclusion: FANCI may be a potential therapeutic target for OVCA patients.

Keywords: DNA damage; FANCD2; FANCI; P53; chemoresistance; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carboplatin / pharmacology
  • Carboplatin / therapeutic use
  • Carcinoma, Ovarian Epithelial
  • DNA Copy Number Variations
  • DNA Damage
  • Fanconi Anemia Complementation Group D2 Protein / chemistry
  • Fanconi Anemia Complementation Group D2 Protein / genetics
  • Fanconi Anemia Complementation Group D2 Protein / metabolism
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia* / drug therapy
  • Fanconi Anemia* / genetics
  • Fanconi Anemia* / metabolism
  • Female
  • Humans
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics


  • FANCI protein, human
  • Fanconi Anemia Complementation Group D2 Protein
  • Fanconi Anemia Complementation Group Proteins
  • Carboplatin

Supplementary concepts

  • Fanconi Anemia, Complementation Group I