PMID- 33122828 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20230530 IS - 1476-5594 (Electronic) IS - 0950-9232 (Linking) VI - 40 IP - 2 DP - 2021 Jan TI - Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1. PG - 246-261 LID - 10.1038/s41388-020-01486-7 [doi] AB - 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. FAU - Jia, Yuefeng AU - Jia Y AD - Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China. FAU - Ding, Xuemei AU - Ding X AD - Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China. FAU - Zhou, Lihua AU - Zhou L AD - Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China. FAU - Zhang, Li AU - Zhang L AD - Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China. FAU - Yang, Xuecheng AU - Yang X AUID- ORCID: 0000-0002-5269-2876 AD - Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China. m18661805062@163.com. LA - eng PT - Journal Article PT - Retracted Publication DEP - 20201029 PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Biomarkers, Tumor) RN - 0 (Cell Cycle Proteins) RN - 0 (MIRN139 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (PRC1 protein, human) SB - IM CIN - J Urol. 2021 Nov;206(5):1319-1321. PMID: 34392697 RIN - Oncogene. 2023 Jul;42(28):2235. PMID: 37253965 MH - Adult MH - Aged MH - Animals MH - Apoptosis MH - Biomarkers, Tumor/genetics/*metabolism MH - Cell Cycle Proteins/genetics/*metabolism MH - Cell Proliferation MH - Exosomes/*genetics MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - MicroRNAs/administration & dosage/*genetics MH - Middle Aged MH - Prognosis MH - Survival Rate MH - Tumor Cells, Cultured MH - Urinary Bladder Neoplasms/genetics/metabolism/pathology/*prevention & control MH - Xenograft Model Antitumor Assays EDAT- 2020/10/31 06:00 MHDA- 2021/04/28 06:00 CRDT- 2020/10/30 05:51 PHST- 2020/02/23 00:00 [received] PHST- 2020/09/21 00:00 [accepted] PHST- 2020/09/10 00:00 [revised] PHST- 2020/10/31 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/10/30 05:51 [entrez] AID - 10.1038/s41388-020-01486-7 [pii] AID - 10.1038/s41388-020-01486-7 [doi] PST - ppublish SO - Oncogene. 2021 Jan;40(2):246-261. doi: 10.1038/s41388-020-01486-7. Epub 2020 Oct 29.