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 DDPresistant 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.

In order to make a comprehensive assessment of the potential association between one genetic variant in the cyclin-dependent kinase inhibitor 1B gene, rs2066827, and breast cancer risk, we conducted a meta-analysis of six epidemiological studies, which included 3,139 breast cancer cases and 2,936 controls. The data showed that rs2066827 polymorphism was not associated with increased breast cancer risk in overall population. When stratifying by the race, no noteworthy associations were observed in Asians or Caucasians. Based on this meta-analysis, we conclude that the cyclin-dependent kinase inhibitor 1B rs2066827 polymorphism might not be a risk factor for breast cancer development. Further studies, either with larger sample size or involving other SNPs and haplotypes of the cyclin-dependent kinase inhibitor 1B gene, are necessary to clarify the contribution of cyclin-dependent kinase inhibitor 1B rs2066827 in breast carcinogenesis.

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