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Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis

BACKGROUND: Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain...

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Autores principales: Dong, Wei, Bi, Junming, Liu, Hongwei, Yan, Dong, He, Qingqing, Zhou, Qianghua, Wang, Qiong, Xie, Ruihui, Su, Yinjie, Yang, Meihua, Lin, Tianxin, Huang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524247/
https://www.ncbi.nlm.nih.gov/pubmed/31101108
http://dx.doi.org/10.1186/s12943-019-1025-z
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author Dong, Wei
Bi, Junming
Liu, Hongwei
Yan, Dong
He, Qingqing
Zhou, Qianghua
Wang, Qiong
Xie, Ruihui
Su, Yinjie
Yang, Meihua
Lin, Tianxin
Huang, Jian
author_facet Dong, Wei
Bi, Junming
Liu, Hongwei
Yan, Dong
He, Qingqing
Zhou, Qianghua
Wang, Qiong
Xie, Ruihui
Su, Yinjie
Yang, Meihua
Lin, Tianxin
Huang, Jian
author_sort Dong, Wei
collection PubMed
description BACKGROUND: Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer. METHODS: circACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs. RESULTS: The expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression. CONCLUSIONS: circACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-019-1025-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-65242472019-05-24 Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis Dong, Wei Bi, Junming Liu, Hongwei Yan, Dong He, Qingqing Zhou, Qianghua Wang, Qiong Xie, Ruihui Su, Yinjie Yang, Meihua Lin, Tianxin Huang, Jian Mol Cancer Research BACKGROUND: Circular RNAs (circRNAs) have been considered to mediate occurrence and development of human cancers, generally acting as microRNA (miRNA) sponges to regulate downstream genes expression. However, the aberrant expression profile and dysfunction of circRNAs in human bladder cancer remain to be investigated. The present study aims to elucidate the potential role and molecular mechanism of circACVR2A in regulating the proliferation and metastasis of bladder cancer. METHODS: circACVR2A (hsa_circ_0001073) was identified by RNA-sequencing and validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. The role of circACVR2A in bladder cancer was assessed both in vitro and in vivo. Biotin-coupled probe pull down assay, biotin-coupled microRNA capture, dual-luciferase reporter assay, and fluorescence in situ hybridization were conducted to evaluate the interaction between circACVR2A and microRNAs. RESULTS: The expression of circACVR2A was lower in bladder cancer tissues and cell lines. The down-regulation of circACVR2A was positively correlated with aggressive clinicopathological characteristics, and circACVR2A served as an independent risk factor for overall survival in bladder cancer patients after cystectomy. Our in vivo and in vitro data indicated that circACVR2A suppressed the proliferation, migration and invasion of bladder cancer cells. Mechanistically, we found that circACVR2A could directly interact with miR-626 and act as a miRNA sponge to regulate EYA4 expression. CONCLUSIONS: circACVR2A functions as a tumor suppressor to inhibit bladder cancer cell proliferation and metastasis through miR-626/EYA4 axis, suggesting that circACVR2A is a potential prognostic biomarker and therapeutic target for bladder cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12943-019-1025-z) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-17 /pmc/articles/PMC6524247/ /pubmed/31101108 http://dx.doi.org/10.1186/s12943-019-1025-z Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Dong, Wei
Bi, Junming
Liu, Hongwei
Yan, Dong
He, Qingqing
Zhou, Qianghua
Wang, Qiong
Xie, Ruihui
Su, Yinjie
Yang, Meihua
Lin, Tianxin
Huang, Jian
Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis
title Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis
title_full Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis
title_fullStr Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis
title_full_unstemmed Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis
title_short Circular RNA ACVR2A suppresses bladder cancer cells proliferation and metastasis through miR-626/EYA4 axis
title_sort circular rna acvr2a suppresses bladder cancer cells proliferation and metastasis through mir-626/eya4 axis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524247/
https://www.ncbi.nlm.nih.gov/pubmed/31101108
http://dx.doi.org/10.1186/s12943-019-1025-z
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