MicroRNA-16 sensitizes breast cancer cells to paclitaxel through suppression of IKBKB expression

Oncotarget. 2016 Apr 26;7(17):23668-83. doi: 10.18632/oncotarget.8056.


Paclitaxel (Taxol) is an effective chemotherapeutic agent for treating breast cancer patients. However, chemoresistance is a major obstacle in cancer treatment. Here, we showed that overexpression of miR-16 promoted Taxol-induced cytotoxicity and apoptosis in breast cancer cells. Furthermore, IκB kinase β (IKBKB) was identified as a direct target of miR-16. Up-regulation of IKBKB suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol, and restoring IKBKB expression in miR-16-overexpressing breast cancer cells recovered Taxol resistance. Moreover, miR-16 was highly expressed in Taxol-sensitive breast cancer tissues compared with Taxol-resistant tissues, and there was an inverse correlation between miR-16 expression and IKBKB expression in breast cancer tissues. The expression levels of miR-16 were negatively associated with T stages, whereas the expression of IKBKB was positively correlated with T stages, lymph node metastasis and clinical stages. Taken together, our data demonstrates that miR-16 sensitizes breast cancer cells to Taxol through the suppression of IKBKB expression, and targeting miR-16/IKBKB axis will be a promising strategy for overcoming Taxol resistance in breast cancer.

Keywords: IKBKB; Taxol; breast cancer; chemosensitivity; miR-16.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / secondary
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / secondary
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness
  • Paclitaxel / pharmacology*
  • Prognosis
  • Survival Rate
  • Tumor Cells, Cultured


  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • MIRN16 microRNA, human
  • MicroRNAs
  • I-kappa B Kinase
  • IKBKB protein, human
  • Paclitaxel