Cancer Management and Research (Sep 2020)
Adipose Mesenchymal Stem Cell-Derived Exosomal microRNA-1236 Reduces Resistance of Breast Cancer Cells to Cisplatin by Suppressing SLC9A1 and the Wnt/β-Catenin Signaling
Abstract
Zhongming Jia,1,* Huamin Zhu,2,* Hongguang Sun,1 Yitong Hua,1 Guoqiang Zhang,1 Jingru Jiang,1 Xiaohong Wang1 1Department of Thyroid and Breast Surgery, Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong, People’s Republic of China; 2Department of Medical Ultrasonics, Affiliated Hospital of Binzhou Medical University, Binzhou 256603, Shandong, People’s Republic of China*These authors contributed equally to this work.Correspondence: Zhongming Jia Tel +86-543-325779Email [email protected]: Emerging evidence has noted the versatile functions of mesenchymal stem cell-derived exosomes (MSC-Exos) in cancer control. This work aims to probe to function of adipose MSC-Exos (adMSC-Exos) in drug-resistance of breast cancer (BC) cells to cisplatin (DDP) and the molecules involved.Methods: Parental and DDP-resistant BC cell lines MCF-7 and MDA-MB-231 were used. All cells were pre-treated with adMSC-Exos. Then, the viability and apoptosis of cells after DDP treatment were determined. Differentially expressed miRNAs after adMSC-exo treatment were screened out. Rescue experiments were conducted by pre-transfecting miR-1236 inhibitor into adMSCs, and the role of miR-1236 in DDP sensitivity was determined. Targeting mRNAs of miR-1236 were predicted by bioinformatics analysis. Altered SLC9A1 expression was administrated to evaluate its function in DDP resistance.Results: The adMSC-Exos notably increased the sensitivity of either parental or DDP-resistant BC cells to DDP. SLC9A1 was notably highly expressed in DDP-resistant cells but inhibited following adMSC-exo administration. Importantly, miR-1236, which could directly bind to SLC9A1 and suppress its expression, was confirmed as an enriched miRNA in adMSC-Exos. Either inhibition of miR-1236 or upregulation of SLC9A1 blocked the pro-sensitize roles of adMSC-Exos. In addition, the Wnt/β-catenin pathway activity was suppressed by adMSC-Exos but recovered by SLC9A1.Conclusion: This study evidenced that adMSC-Exos carry miR-1236 to increase sensitivity of BC cells to DDP with the involvement of SLC9A1 downregulation and Wnt/β-catenin inactivation. This finding may offer novel insights into treatment for drug-resistant BC.Keywords: breast cancer, cisplatin, resistance, adipose mesenchymal stem cell-derived exosomes, microRNA-1236, SLC9A1
