Exploring Specific miRNA-mRNA Axes With Relationship to Taxanes-Resistance in Breast Cancer

• Main Authors: Danni Chen, Chang Bao, Feng Zhao, Haogang Yu, Guansheng Zhong, Liang Xu, Senxiang Yan
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-08-01
• Series: Frontiers in Oncology
• Subjects: breast cancer; taxanes-resistance; miR-335-5p/CXCL9 axis; let-7c-5p/CCR7/SOCS1 axis; WCGNA
• Online Access: https://www.frontiersin.org/article/10.3389/fonc.2020.01397/full

Breast cancer is the most prevalent type of malignancy in women worldwide. Taxanes (paclitaxel and docetaxel) are widely applied as first-line chemotherapeutic agents, while the therapeutic effect is seriously limited by the development of drug resistance. In the present study, we screened out several miRNAs dysregulated in taxanes-resistant breast cancer samples and confirmed that two miRNAs (miR-335-5p and let-7c-5p) played a major role in cell proliferation, apoptosis, and chemo-resistance. In addition, the weighted gene co-expression network analysis (WGCNA) for potential target genes of miR-335-5p and let-7c-5p identified three hub genes (CXCL9, CCR7, and SOCS1) with a positive relationship to taxanes-sensitivity. Further, target relationships between miR-335-5p and CXCL9, let-7c-5p and CCR7/SOCS1 were confirmed by dual-luciferase reporter assays. Importantly, the regulatory functions of CXCL9, CCR7, and SOCS1 on proliferation and chemoresistance were validated. In conclusion, our study shed light on clinical theragnostic relationships between miR-335-5p/CXCL9, let-7c-5p/CCR7/SOCS1 axes, and taxanes-resistance in breast cancer.