MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression

Jiang,Hua; Cheng,Lin; Hu,Pan; Liu,Renbin

doi:10.3892/mmr.2018.9064

MicroRNA‑663b mediates TAM resistance in breast cancer by modulating TP73 expression

Authors:
- Hua Jiang
- Lin Cheng
- Pan Hu
- Renbin Liu
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Affiliations: Breast Cancer Center, Department of Breast and Thyroid Surgery, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/mmr.2018.9064
Pages: 1120-1126

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Abstract

Breast cancer is the second leading cause of cancer‑associated mortalities in women. Tamoxifen (TAM) is an endocrine therapy commonly used in the treatment of patients with breast cancer expressing estrogen receptor α. However, treatment often ends in failure due to the emergence of drug resistance. MicroRNAs (miRNAs), a family of small non‑coding RNAs, serve critical roles in the regulation of gene expression and cell events. To date, whether miRNA‑663b could mediate TAM resistance in breast cancer remains unknown. Therefore, the aim of the present study was to investigate the role of miRNA‑663b in TAM resistance in breast cancer. The results demonstrated that miRNA‑663b was upregulated in breast cancer with TAM resistance. Tumor protein 73 (TP73) was a direct target of miRNA‑663b, and was negatively regulated by miRNA‑663b in MCF‑7 cells. Furthermore, it was identified that downregulation of miRNA‑663b inhibited cell proliferation ability and promoted cell apoptosis, resulting in enhanced TAM sensitivity. In addition, these findings suggested that TP73 silencing may have eliminated the effects of miRNA‑663b inhibitor on breast cancer cells. In conclusion, the present study verified a novel molecular link between miRNA‑663b and TP73, and indicated that miRNA‑663b may be a critical therapeutic target in breast cancer.

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