Mesenchymal stem cells-derived exosomal microRNA-139-5p restrains tumorigenesis in bladder cancer by targeting PRC1
Authors: Yuefeng Jia
Xuecheng Yang
Lihua Zhou
Li Zhang
Xuemei Ding
Journal: Oncogene (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: microRNAs; tumor cells; mesenchymal stem cells (MSCs); exosomes; miR-139-5p
Affiliations: Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China., Department of Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China., Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China., Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, PR China. .

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. 

Retracted: No

PubPeer comments:
 The article refers to PRC1 as the Polycomb Repressor Complex 1. PRC1 in this case is a complex of proteins involved in epitransciptomics, it s not one single protein. There is one individual protein called PRC1 that refers to protein regulator of cytokinesis 1. The antibody used in this study as well as the primers sequences seem to target the regulator of cytokinesis. The antibody per se has been used by multiple labs to detect the regulator of cytokinesis ( https: www.abcam.com prc1-antibody-ep1513y-ab51248.html) Here is the alignment between the miRNA and the sequence targeted in PRC1: Homo sapiens protein regulator of cytokinesis 1 (PRC1), transcript variant 2, mRNA Sequence ID: NM_199413.3Length: 3030Number of Matches: 1 Range 1: 2248 to 2267 ScoretExpecttIdentitiestGapstStrand 40.1 bits(20)t0.75t20 20(100%)t0 20(0%)tPlus Plus Query 2 TTTTATTTCACCACTGTAGG 21 Sbjct 2248 TTTTATTTCACCACTGTAGG 2267 Then, I thought that the authors meant to talk about the regulator of cytokinesis but in multiple paragraphs, they discussed the involvement of the polycomb repressor complex and other proteins from this complex in bladder cancer, like in the discussion: A polycomb group protein, BMI1 is a member of PRC1, playing an oncogenic role in prostate cancer through strengthening the enzymatic activities of RING1B. Moreover, Zhu and his colleges have reported a PRC1-independent role of BMI1 [25]. Silencing of BMI1 exerts tumor-suppressive functions by blocking cell cycle at G1 phase and inducing apoptosis [26]. Reference 25 is about the regulator of cytokinesis, reference 26 is about the polycomb repressor complex 1. I m just not sure if the authors realize that PRC1 could refer to 2 different things and are mixing all the information about the repressor of cytokinesis and the repressor but this is highly confusing. , 
 Fig 7c,  Representative images of transplanted tumors in tumor-bearing nude mice, n = 15 . ![file] The same distinctively-scratched ruler appears in at least two other tumor identity parades: Fig 7B of [Li et al (2021)] ,  representative images of tumours , and Fig 6B from [Li et al (2021a)] .  Representative images of dissected tumours from nude mice and tumour weight from different groups . ![] Here in context: ![] ![] --------------------------------------------- UPDATE Two more sightings from Figs 3i, 5h of [Zhou et al (2020)] .  Representative macroscopic image of a xenograft tumor after treatment with oe-circ_002117 or oe-NC ;  Representative xenograft tumor pictures upon treatment with miR-370 mimic, miR-370 inhibitor or controls . ![] Fig 6A of [Xin et al (2021)] , Fig 6A.  Representative macroscopic images of xenograft tumor formation in nude mice . ![] Fig 5a from [Chang et al (2021)] ,  Representative images showing xenografts in nude mice treated with U251MG cells transfected with either oe-RP11-84E24.3 or si-RP11-84E24.3 . ![] ,