MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene

MiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found...

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Main Authors: Hongbo Luo, Rui Yang, Chun Li, Yongqing Tong, Lingling Fan, Xiuheng Liu, Chuanrui Xu
Format: Article
Language:English
Published: SAGE Publishing 2017-07-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317718414
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author Hongbo Luo
Rui Yang
Chun Li
Yongqing Tong
Lingling Fan
Xiuheng Liu
Chuanrui Xu
author_facet Hongbo Luo
Rui Yang
Chun Li
Yongqing Tong
Lingling Fan
Xiuheng Liu
Chuanrui Xu
author_sort Hongbo Luo
collection DOAJ
description MiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3′ untranslated region of Bmi1 messenger RNA. Stem cell–related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked self-renewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.
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publisher SAGE Publishing
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series Tumor Biology
spelling doaj-art-d5c90e5ff7484a919e8b21000c926beb2025-08-02T20:28:43ZengSAGE PublishingTumor Biology1423-03802017-07-013910.1177/1010428317718414MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogeneHongbo Luo0Rui Yang1Chun Li2Yongqing Tong3Lingling Fan4Xiuheng Liu5Chuanrui Xu6Department of Urology, Renmin Hospital of Wuhan University, Wuhan, P.R. ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, P.R. ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Clinical Laboratory, Renmin Hospital of Wuhan University, Wuhan, P.R. ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaDepartment of Urology, Renmin Hospital of Wuhan University, Wuhan, P.R. ChinaSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. ChinaMiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3′ untranslated region of Bmi1 messenger RNA. Stem cell–related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked self-renewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.https://doi.org/10.1177/1010428317718414
spellingShingle Hongbo Luo
Rui Yang
Chun Li
Yongqing Tong
Lingling Fan
Xiuheng Liu
Chuanrui Xu
MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
Tumor Biology
title MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
title_full MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
title_fullStr MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
title_full_unstemmed MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
title_short MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
title_sort microrna 139 5p inhibits bladder cancer proliferation and self renewal by targeting the bmi1 oncogene
url https://doi.org/10.1177/1010428317718414
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AT ruiyang microrna1395pinhibitsbladdercancerproliferationandselfrenewalbytargetingthebmi1oncogene
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AT yongqingtong microrna1395pinhibitsbladdercancerproliferationandselfrenewalbytargetingthebmi1oncogene
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AT xiuhengliu microrna1395pinhibitsbladdercancerproliferationandselfrenewalbytargetingthebmi1oncogene
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