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

Abstract

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.

• Authors: Xueyuan Tang, Long Jin, Peiguo Cao, Ke Cao, Chenghui Huang, Yanwei Luo, Jian Ma, Shourong Shen, Ming Tan, Xiayu Li, Ming Zhou
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 17 Pg. 23668-83 (Apr 26 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 26993770 (Publication Type: Journal Article)

Chemical References

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

Topics

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