The inhibition of UBC13 expression and blockage of the DNMT1-CHFR-Aurora A pathway contribute to paclitaxel resistance in ovarian cancer

Cell Death Dis. 2018 Jan 24;9(2):93. doi: 10.1038/s41419-017-0137-x.


Paclitaxel is widely used as a first-line chemotherapeutic drug for patients with ovarian cancer and other solid cancers, but drug resistance occurs frequently, resulting in ovarian cancer still presenting as the highest lethality among all gynecological tumors. Here, using DIGE quantitative proteomics, we identified UBC13 as down-regulated in paclitaxel-resistant ovarian cancer cells, and it was further revealed by immunohistochemical staining that UBC13 low-expression was associated with poorer prognosis and shorter survival of the patients. Through gene function experiments, we found that paclitaxel exposure induced UBC13 down-regulation, and the enforced change in UBC13 expression altered the sensitivity to paclitaxel. Meanwhile, the reduction of UBC13 increased DNMT1 levels by attenuating its ubiquitination, and the up-regulated DNMT1 enhanced the CHFR promoter DNA methylation levels, leading to a reduction of CHFR expression, and an increased in the levels of Aurora A. Our findings revealed a novel function for UBC13 in regulating paclitaxel sensitivity through a DNMT1-CHFR-Aurora A pathway in ovarian cancer cells. UBC13 could potentially be employed as a therapeutic molecular drug for reversing paclitaxel resistance in ovarian cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aurora Kinase A / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • DNA (Cytosine-5-)-Methyltransferase 1 / metabolism*
  • DNA Methylation / genetics
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Enzyme Stability / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / pharmacology*
  • Poly-ADP-Ribose Binding Proteins / metabolism*
  • Prognosis
  • Promoter Regions, Genetic
  • Proteomics
  • Ubiquitin-Conjugating Enzymes / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination


  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Poly-ADP-Ribose Binding Proteins
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNMT1 protein, human
  • UBE2N protein, human
  • Ubiquitin-Conjugating Enzymes
  • CHFR protein, human
  • Ubiquitin-Protein Ligases
  • Aurora Kinase A
  • Paclitaxel