Background: 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.
CITATION STYLE
Jia, Z., Zhu, H., Sun, H., Hua, Y., Zhang, G., Jiang, J., & Wang, X. (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. Cancer Management and Research, 12, 8733–8744. https://doi.org/10.2147/CMAR.S270200
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