Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression

Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal ur...

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Main Authors: Feifan Wang, Mengjing Fan, Yueshu Cai, Xuejian Zhou, Shengcheng Tai, Yanlan Yu, Hongshen Wu, Yan Zhang, Jiaxin Liu, Shihan Huang, Ning He, Zhenghui Hu, Xiaodong Jin
Format: Article
Language:English
Published: Elsevier 2020-12-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253120303152
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author Feifan Wang
Mengjing Fan
Yueshu Cai
Xuejian Zhou
Shengcheng Tai
Yanlan Yu
Hongshen Wu
Yan Zhang
Jiaxin Liu
Shihan Huang
Ning He
Zhenghui Hu
Xiaodong Jin
author_facet Feifan Wang
Mengjing Fan
Yueshu Cai
Xuejian Zhou
Shengcheng Tai
Yanlan Yu
Hongshen Wu
Yan Zhang
Jiaxin Liu
Shihan Huang
Ning He
Zhenghui Hu
Xiaodong Jin
author_sort Feifan Wang
collection DOAJ
description Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.
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spelling doaj.art-c3c7622cdb044007b048785efaa9ef092022-12-21T22:48:41ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-12-0122815831Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 ExpressionFeifan Wang0Mengjing Fan1Yueshu Cai2Xuejian Zhou3Shengcheng Tai4Yanlan Yu5Hongshen Wu6Yan Zhang7Jiaxin Liu8Shihan Huang9Ning He10Zhenghui Hu11Xiaodong Jin12Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Pathology, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China; Department of Urology, Xiaoshan Hospital, Hangzhou, Zhejiang 311200, PR ChinaDepartment of Urology, Sir Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR ChinaDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China; Corresponding author: Xiaodong Jin, Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, PR China.Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.http://www.sciencedirect.com/science/article/pii/S2162253120303152circRIMS1bladder cancermiR-433-3pCCAR1progression
spellingShingle Feifan Wang
Mengjing Fan
Yueshu Cai
Xuejian Zhou
Shengcheng Tai
Yanlan Yu
Hongshen Wu
Yan Zhang
Jiaxin Liu
Shihan Huang
Ning He
Zhenghui Hu
Xiaodong Jin
Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression
Molecular Therapy: Nucleic Acids
circRIMS1
bladder cancer
miR-433-3p
CCAR1
progression
title Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression
title_full Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression
title_fullStr Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression
title_full_unstemmed Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression
title_short Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression
title_sort circular rna circrims1 acts as a sponge of mir 433 3p to promote bladder cancer progression by regulating ccar1 expression
topic circRIMS1
bladder cancer
miR-433-3p
CCAR1
progression
url http://www.sciencedirect.com/science/article/pii/S2162253120303152
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