Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1 (Retracted Article)
Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1 (Retracted Article)
复制标题
DOI：
10.1038/s41388-020-01486-7
复制
发表时间：
2020-10-29
期刊：
影响因子：
8
通讯作者：
Yang, Xuecheng
中科院分区：
文献类型：
--
作者：
Jia, Yuefeng;Ding, Xuemei;Yang, Xuecheng
microRNA（miRNAs）可以被递送到肿瘤细胞，在肿瘤细胞中它们通过间充质干细胞（MSC）衍生的外泌体发挥其功能。本研究探讨了miR-139- 5 p向膀胱癌细胞的外泌体转移及其在肿瘤发生中的调节作用。通过RNA定量表征膀胱癌中多梳阻遏复合物1（PRC 1）的失调，并通过功能丧失实验鉴定其在膀胱癌细胞中的功能意义。我们预测了miR-139- 5 p可能在PRC 1的调控中发挥作用，并通过双荧光素酶报告基因分析进一步验证了这一点。接下来，我们改变了膀胱癌细胞中miR-139- 5 p和PRC 1的表达，以确定它们在癌症进展中的功能。将膀胱癌细胞与从过表达miR-139- 5 p的人脐带间充质干细胞（hUCMSC）分离的外来体共培养。使用功能获得和功能丧失方法确定miR-139- 5 p的细胞间转移沿着体外和体内功能。我们的研究结果表明，PRC 1水平在膀胱癌组织和细胞中增加，沉默PRC 1似乎阻碍细胞增殖，迁移和侵袭潜力。此外，观察到miR-139- 5 p在膀胱癌中下调，其靶向PRC 1并降低其表达，从而导致膀胱癌细胞体外致瘤特性的改善。此外，我们注意到来自hUCMSC衍生的外泌体的miR-139- 5 p可以转移到膀胱癌细胞中以下调PRC 1表达。此外，hUCMSC衍生的外泌体miR-139- 5 p在体外和体内对膀胱癌发展具有抑制作用。这些数据共同支持MSC衍生的外泌体miR-139- 5 p在膀胱癌中的肿瘤抑制作用，突出了一种有希望的治疗策略。
microRNAs (miRNAs) can be delivered to tumor cells where they exert their function via mesenchymal stem cells (MSCs)-derived exosomes. This study investigated exosomal transfer of miR-139-5p to bladder cancer cells and their role in the regulation of tumorigenesis. The dysregulation of polycomb repressor complex 1 (PRC1) in bladder cancer was characterized by RNA quantification, and its functional significance in bladder cancer cells was identified by loss-of-function experiments. We predicted the miR-139-5p that could play a role in regulating PRC1, which was further verified using dual-luciferase reporter gene assay. Next, we altered the expression of miR-139-5p and PRC1 in bladder cancer cells to identify their functions in cancer progression. Bladder cancer cells were co-cultured with exosomes isolated from human umbilical cord mesenchymal stem cells (hUCMSCs) over-expressing miR-139-5p. The intercellular transfer of miR-139-5p along with in vitro and in vivo functions was determined using gain- and loss-of-function approaches. Our results revealed that PRC1 levels were increased in bladder cancer tissues and cells, and silencing PRC1 appeared to impede the cell proliferation, migration, and invasion potentials. In addition, miR-139-5p was observed to be down-regulated in bladder cancer, which targeted PRC1 and reduced its expression, hereby resulting in ameliorated tumorigenic characteristics of bladder cancer cells in vitro. Furthermore, we noted that miR-139-5p from hUCMSCs-derived exosomes could be transferred into bladder cancer cells to down-regulate the PRC1 expression. Moreover, hUCMSCs-derived exosomal miR-139-5p conferred a suppressive role on bladder cancer development in vitro and in vivo. These data together supported the tumor-inhibiting role of MSCs-derived exosomal miR-139-5p in bladder cancer, highlighting a promising therapeutic strategy.