MiR-18a upregulation decreases Dicer expression and confers paclitaxel resistance in triple negative breast cancer

L.-Y. Sha, Y. Zhang, W. Wang, X. Sui, S.-K. Liu, T. Wang, H. Zhang

Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Huizhange@outlook.com

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• Oncology

OBJECTIVE: MiR-18a is a miRNA that is aberrantly overexpressed in triple-negative breast cancer (TNBC). However, its biophysical function in TNBC is still not clear. In this study, we investigated the association among miR-18a dysregulation, Dicer dysregulation and paclitaxel (PTX) resistance in TNBC cells.

PATIENTS AND METHODS: 20 TNBC patients who received neoadjuvant chemotherapy before surgery were recruited. MiR-18a expression was quantified using QRT-PCR. The effects of miR-18a overexpression or knockdown on cell viability and apoptosis of PTX sensitive MDA-MB-231 cells and PTX resistant MDA-MB-231 cells after PTX treatment were studied. The influence of miR-18a overexpression on Dicer expression was measured by qRT-PCR and Western blot analysis.

RESULTS: Tissues from patients with stable disease (SD, n = 5) and progressive disease (PD, n = 2) to paclitaxel (PTX) containing neoadjuvant chemotherapy had significantly higher miR-18a expression than that from patients with partial response (PR, n = 13). MDA-MB-231/PTX cells had higher miR-18a expression than MDA-MB-231 cells. MiR-18a overexpression directly led to Dicer repression at mRNA and protein level. MiR-18a overexpression significantly increased PTX IC50 and reduced PTX induced cell apoptosis, while miR-18a suppression substantially decreased PTX IC50 and increased PTX induced cell apoptosis.

CONCLUSIONS: This study found that miR-18a is an important miRNA that suppresses Dicer expression and increases PTX resistance in TNBC cells.

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