Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1

Abstract Bladder Cancer (BC) is the ninth most common tumor in the world and one of the most common malignant tumors of the urinary system. Some studies reported that miR‐133b expression is reduced in BC, but whether it plays a role in the development of BC and its mechanism is unclear. microRNAs ca...

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Main Authors: Xiaoxiao Cai, Lili Qu, Jian Yang, Junwen Xu, Li Sun, Xiaowei Wei, Xiaojun Qu, Tingting Bai, Zhirui Guo, Yefei Zhu
Format: Article
Language:English
Published: Wiley 2020-08-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.3263
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author Xiaoxiao Cai
Lili Qu
Jian Yang
Junwen Xu
Li Sun
Xiaowei Wei
Xiaojun Qu
Tingting Bai
Zhirui Guo
Yefei Zhu
author_facet Xiaoxiao Cai
Lili Qu
Jian Yang
Junwen Xu
Li Sun
Xiaowei Wei
Xiaojun Qu
Tingting Bai
Zhirui Guo
Yefei Zhu
author_sort Xiaoxiao Cai
collection DOAJ
description Abstract Bladder Cancer (BC) is the ninth most common tumor in the world and one of the most common malignant tumors of the urinary system. Some studies reported that miR‐133b expression is reduced in BC, but whether it plays a role in the development of BC and its mechanism is unclear. microRNAs can be packaged into exosomes to mediate communication between tumor cells, affecting their proliferation and apoptosis. The objective of this study was to investigate the effect of exosomal miR‐133b on BC proliferation and its molecular mechanism. Firstly, the expression of miR‐133b was evaluated in BC and adjacent normal tissues, as well as in serum exosomes of BC patients and healthy controls. Then the delivery and internalization of exosomes in cells was observed through fluorescence localization. Cell viability and apoptosis were assessed in BC cells transfected with mimics and incubated with exosomes. The role of exosomal miR‐133b was also analyzed in nude mice transplant tumors. Furthermore, the target gene of miR‐133b was predicted through bioinformatics. The level of miR‐133b was significantly decreased in BC tissues and in exosomes from serum of patients, which was correlated with poor overall survival in TCGA. Exosomal miR‐133b could be obtained using BC cells after transfection with miR‐133b mimics. The miR‐133b expression increased after incubation with exosomal miR‐133b, which lead to the inhibition of viability and increase of apoptosis in BC cells. Exosomal miR‐133b could suppress tumor growth in vivo. In addition, we found that exosomal miR‐133b may play a role in suppressing BC proliferation by upregulating dual‐specificity protein phosphatase 1 (DUSP1). These findings may offer promise for new therapeutic directions of BC.
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spelling doaj.art-5dd7e10b69d64444875cdd9658c1b9092023-12-18T12:56:30ZengWileyCancer Medicine2045-76342020-08-019166009601910.1002/cam4.3263Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1Xiaoxiao Cai0Lili Qu1Jian Yang2Junwen Xu3Li Sun4Xiaowei Wei5Xiaojun Qu6Tingting Bai7Zhirui Guo8Yefei Zhu9Laboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaLaboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaUrinary SurgeryThe Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaLaboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaLaboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaLaboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaLaboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaGerontology Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaGerontology Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaLaboratory Medicine Center The Second Affiliated HospitalNanjing Medical University Nanjing Jiangsu ChinaAbstract Bladder Cancer (BC) is the ninth most common tumor in the world and one of the most common malignant tumors of the urinary system. Some studies reported that miR‐133b expression is reduced in BC, but whether it plays a role in the development of BC and its mechanism is unclear. microRNAs can be packaged into exosomes to mediate communication between tumor cells, affecting their proliferation and apoptosis. The objective of this study was to investigate the effect of exosomal miR‐133b on BC proliferation and its molecular mechanism. Firstly, the expression of miR‐133b was evaluated in BC and adjacent normal tissues, as well as in serum exosomes of BC patients and healthy controls. Then the delivery and internalization of exosomes in cells was observed through fluorescence localization. Cell viability and apoptosis were assessed in BC cells transfected with mimics and incubated with exosomes. The role of exosomal miR‐133b was also analyzed in nude mice transplant tumors. Furthermore, the target gene of miR‐133b was predicted through bioinformatics. The level of miR‐133b was significantly decreased in BC tissues and in exosomes from serum of patients, which was correlated with poor overall survival in TCGA. Exosomal miR‐133b could be obtained using BC cells after transfection with miR‐133b mimics. The miR‐133b expression increased after incubation with exosomal miR‐133b, which lead to the inhibition of viability and increase of apoptosis in BC cells. Exosomal miR‐133b could suppress tumor growth in vivo. In addition, we found that exosomal miR‐133b may play a role in suppressing BC proliferation by upregulating dual‐specificity protein phosphatase 1 (DUSP1). These findings may offer promise for new therapeutic directions of BC.https://doi.org/10.1002/cam4.3263Bladder cancerDual‐specificity protein phosphatase 1ExosomemicroRNA‐133bProliferation
spellingShingle Xiaoxiao Cai
Lili Qu
Jian Yang
Junwen Xu
Li Sun
Xiaowei Wei
Xiaojun Qu
Tingting Bai
Zhirui Guo
Yefei Zhu
Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1
Cancer Medicine
Bladder cancer
Dual‐specificity protein phosphatase 1
Exosome
microRNA‐133b
Proliferation
title Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1
title_full Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1
title_fullStr Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1
title_full_unstemmed Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1
title_short Exosome–transmitted microRNA‐133b inhibited bladder cancer proliferation by upregulating dual‐specificity protein phosphatase 1
title_sort exosome transmitted microrna 133b inhibited bladder cancer proliferation by upregulating dual specificity protein phosphatase 1
topic Bladder cancer
Dual‐specificity protein phosphatase 1
Exosome
microRNA‐133b
Proliferation
url https://doi.org/10.1002/cam4.3263
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