Background

Donor cell-derived exosomes regulate recipient cell functions. The aim of this study was to investigate the effect of human normal bladder stromal cell (hBSC) derived exosomal miR-217 on bladder cell cancer proliferation and migration.

Methods

Human BSCs were transfected with miR-217 mimic or inhibitor and hBSC-derived exosomes were isolated. Human bladder cancer cell lines (T24 and 5367) were co-cultured with hBSC-derived exosomal miR-217 mimic or inhibitor. Proliferation, migration, and apoptosis of the bladder cancer cells were assessed by Edu assay, Transwell migration assay, and Annexin V assay.

Results

Expression of miR-217 was significantly higher in the T24 and 5367 cell lines (P < 0.01). Exosomal miR-217 mimic enhanced proliferation and migration of T24 and 5367 cells, but inhibited apoptosis of the cells (P < 0.01); in contrast, exosomal miR-217 inhibitor suppressed proliferation and migration but stimulated apoptosis of the two cancer cell lines (P < 0.01). Moreover, exosomal miR-217 mimic stimulated YAP and its target proteins including Cyr61, CTGF, and ANKRD1 (P < 0.01), and in contrast, exosomal miR-217 inhibitor suppressed YAP and its target proteins (P < 0.01).

Conclusion

These findings suggested that hBSC-derived exosomal miR-217 may act as oncogene in bladder cancer cells, and that Hippo-YAP signaling pathway maybe the target for miR-217 in the bladder cancer cell lines.

中文翻译：

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膀胱间充质基质细胞衍生的外泌体 miRNA-217 通过 Hippo-YAP 通路调节膀胱癌细胞存活

背景

供体细胞衍生的外泌体调节受体细胞功能。本研究的目的是研究人正常膀胱基质细胞 (hBSC) 衍生的外泌体 miR-217 对膀胱细胞癌增殖和迁移的影响。

方法

用 miR-217 模拟物或抑制剂转染人类 BSC，并分离 hBSC 衍生的外泌体。人膀​​胱癌细胞系（T24 和 5367）与 hBSC 衍生的外泌体 miR-217 模拟物或抑制剂共培养。通过Edu试验、Transwell迁移试验和Annexin V试验评估膀胱癌细胞的增殖、迁移和凋亡。

结果

miR-217 在 T24 和 5367 细胞系中的表达显着升高（P  < 0.01）。外泌体miR-217模拟物增强T24和5367细胞的增殖和迁移，但抑制细胞凋亡（P  < 0.01）；相比之下，外泌体 miR-217 抑制剂抑制增殖和迁移，但刺激两种癌细胞系的凋亡（P  < 0.01）。此外，外泌体 miR-217 模拟物刺激 YAP 及其靶蛋白，包括 Cyr61、CTGF 和 ANKRD1（P  < 0.01），相反，外泌体 miR-217 抑制剂抑制 YAP 及其靶蛋白（P  < 0.01）。

结论

这些发现表明 hBSC 衍生的外泌体 miR-217 可能作为膀胱癌细胞中的癌基因，并且 Hippo-YAP 信号通路可能是膀胱癌细胞系中 miR-217 的靶标。