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RETRACTED ARTICLE: Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1

Oncogene volume 40, pages 246–261 (2021)Cite this article

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This article was retracted on 30 May 2023

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Abstract

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.

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Fig. 1: PRC1 is dysregulated in bladder cancer.
Fig. 2: PRC1 silencing impedes proliferative potential but facilitates apoptosis of bladder cancer cells.
Fig. 3: miR-139-5p targets and negatively modulates PRC1.
Fig. 4: The inhibitory effects of miR-139-5p on the progression of bladder cancer are achieved by negative modulation of PRC1.
Fig. 5: Identification of exosomes derived from hUCMSCs.
Fig. 6: hUCMSCs-derived exosomal miR-139-5p restrains proliferative potential and induces apoptosis of bladder cancer cells.
Fig. 7: The delivery of miR-139-5p from hUCMSCs-derived exosomes curbs tumorigenicity of bladder cancer cells in nude mice.
Fig. 8: Schematic diagram depicting the function and underlying molecular mechanism of miR-139-5p in bladder cancer.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable efforts and comments on this paper.

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Authors and Affiliations

  1. Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China

    Yuefeng Jia & Xuecheng Yang

  2. Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China

    Xuemei Ding & Li Zhang

  3. Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China

    Lihua Zhou

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Correspondence to Xuecheng Yang.

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Jia, Y., Ding, X., Zhou, L. et al. RETRACTED ARTICLE: Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1. Oncogene 40, 246–261 (2021). https://doi.org/10.1038/s41388-020-01486-7

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