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Bladder mesenchymal stromal cell-derived exosomal miRNA-217 modulates bladder cancer cell survival through Hippo-YAP pathway

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Abstract

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.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

hBSC:

Human normal bladder stromal cell

YAP:

Yes-associated proteins

TAZ:

Transcriptional activator with PDZ domain

Cyr 61:

Cysteine-rich protein 61

CTGF:

Connective tissue growth factor

ANKRD1:

Ankyrin repeat domain 1

FCS:

Fetal calf serum

DMEM:

Dulbecco’s modified Eagle’s medium

SV-HUC-1:

Normal human bladder epithelial cell line

TEM:

Transmission electron microscopy

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Authors and Affiliations

  1. Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No.1 Shuaifuyuan Wangfujing, Dongcheng, Beijing, 100730, China

    Zhong-Ming Huang, Hai Wang & Zhi-Gang Ji

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  1. Zhong-Ming Huang
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Contributions

ZMH and ZGJ contributed to the conception and design of the study; ZMH contributed to the acquisition of data and performed the experiments; HW contributed to the analysis of data; ZMH wrote the manuscript; all authors reviewed and approved the final version of the manuscript.

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Correspondence to Zhi-Gang Ji.

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The authors declare that they have no competing interests.

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This research was approved by the Ethics Committee of Peking Union Medical College Hospital. All methods were carried out in accordance with relevant guidelines and regulations. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Huang, ZM., Wang, H. & Ji, ZG. Bladder mesenchymal stromal cell-derived exosomal miRNA-217 modulates bladder cancer cell survival through Hippo-YAP pathway. Inflamm. Res. 70, 959–969 (2021). https://doi.org/10.1007/s00011-021-01494-7

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